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Abnormalities within CD4 and CD8 T lymphocytes subsets in type 1 (insulin-dependent) diabetes.

https://arctichealth.org/en/permalink/ahliterature37074
Source
Clin Exp Immunol. 1991 Aug;85(2):278-81
Publication Type
Article
Date
Aug-1991
Author
J. Ilonen
H M Surcel
M L Käär
Author Affiliation
Department of Medical Microbiology, University of Oulu, Finland.
Source
Clin Exp Immunol. 1991 Aug;85(2):278-81
Date
Aug-1991
Language
English
Publication Type
Article
Keywords
Adolescent
Antigens, CD
Antigens, CD4
Antigens, CD45
Antigens, CD8
Antigens, Differentiation, T-Lymphocyte
CD4-Positive T-Lymphocytes - immunology
Child
Diabetes Mellitus, Type 1 - immunology
Female
Histocompatibility Antigens
Humans
Macrophage-1 Antigen
Male
Research Support, Non-U.S. Gov't
T-Lymphocyte Subsets - immunology
Abstract
Abnormalities in the proportions of various T lymphocyte subpopulations have been found in a number of autoimmune diseases. Monoclonal antibodies labelled with various fluorochromes were used here to define the percentages of subsets, and especially to divide CD4+ (helper/inducer) and CD8+ (suppressor/cytotoxic) cells into phenotypic subgroups. Blood samples were analysed from 25 patients (age 10.1 +/- 3.7 years) with recently diagnosed insulin-dependent diabetes mellitus (IDDM) and 25 age- and sex-matched control subjects. The percentages of CD4+ cells and CD4+CD45RA+ cells described as naive T helper cells or suppressor/inducers were increased in the IDDM patients (P less than 0.05 and P less than 0.05. Student's t-test, respectively), whereas the percentage of CD4+CD45RA- cells (memory T-helper cells, helper/inducers) was similar in the patients and controls. The percentage of CD8+CD11b+ cells containing suppressor/effector lymphocytes was decreased in the IDDM patients as compared with the controls (P less than 0.01) but no significant difference was seen in total CD8+ cells. The percentages of CD3+ cells and the proportions of these simultaneously positive for HLA-DR antigen (activated T cells) were also increased in the recent IDDM patients (P less than 0.001 and P less than 0.05, respectively), while the proportion of CD20+ B cells was decreased (P less than 0.05). The findings support the view that disturbed immune regulation occurs in IDDM and indicate that further division of T cell subpopulations may clarify our understanding of the disease process.
PubMed ID
1677834 View in PubMed
Less detail

Endogenous and recombinant type I interferons and disease activity in multiple sclerosis.

https://arctichealth.org/en/permalink/ahliterature123419
Source
PLoS One. 2012;7(6):e35927
Publication Type
Article
Date
2012
Author
Finn Sellebjerg
Martin Krakauer
Signe Limborg
Dan Hesse
Henrik Lund
Annika Langkilde
Helle Bach Søndergaard
Per Soelberg Sørensen
Author Affiliation
Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. sellebjerg@dadlnet.dk
Source
PLoS One. 2012;7(6):e35927
Date
2012
Language
English
Publication Type
Article
Keywords
Adult
Antigens, CD - immunology
CD4-Positive T-Lymphocytes - immunology
Dendritic Cells
Denmark
Female
Flow Cytometry
HLA-DR Antigens - immunology
Humans
Immunotherapy - methods
Integrin alpha4 - immunology
Interferon Type I - immunology
Interferon-beta - immunology - therapeutic use
Magnetic Resonance Imaging
Male
Middle Aged
Monocytes
Multiple Sclerosis - drug therapy - immunology
Receptors, Transferrin - immunology
Recombinant Proteins - immunology
Statistics, nonparametric
T-Lymphocyte Subsets - immunology
Abstract
Although treatment of multiple sclerosis (MS) with the type I interferon (IFN) IFN-ß lowers disease activity, the role of endogenous type I IFN in MS remains controversial. We studied CD4+ T cells and CD4+ T cell subsets, monocytes and dendritic cells by flow cytometry and analysed the relationship with endogenous type I IFN-like activity, the effect of IFN-ß therapy, and clinical and magnetic resonance imaging (MRI) disease activity in MS patients. Endogenous type I IFN activity was associated with decreased expression of the integrin subunit CD49d (VLA-4) on CD4+CD26(high) T cells (Th1 helper cells), and this effect was associated with less MRI disease activity. IFN-ß therapy reduced CD49d expression on CD4+CD26(high) T cells, and the percentage of CD4+CD26(high) T cells that were CD49d(high) correlated with clinical and MRI disease activity in patients treated with IFN-ß. Treatment with IFN-ß also increased the percentage of CD4+ T cells expressing CD71 and HLA-DR (activated T cells), and this was associated with an increased risk of clinical disease activity. In contrast, induction of CD71 and HLA-DR was not observed in untreated MS patients with evidence of endogenous type IFN I activity. In conclusion, the effects of IFN-ß treatment and endogenous type I IFN activity on VLA-4 expression are similar and associated with control of disease activity. However, immune-activating effects of treatment with IFN-ß may counteract the beneficial effects of treatment and cause an insufficient response to therapy.
Notes
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PubMed ID
22701554 View in PubMed
Less detail

Evidence of an immune-mediated mechanism for an idiosyncratic nevirapine-induced reaction in the female Brown Norway rat.

https://arctichealth.org/en/permalink/ahliterature83006
Source
Chem Res Toxicol. 2005 Dec;18(12):1799-813
Publication Type
Article
Date
Dec-2005
Author
Shenton Jacintha M
Popovic Marija
Chen Jie
Masson Mary Jane
Uetrecht Jack P
Author Affiliation
Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
Source
Chem Res Toxicol. 2005 Dec;18(12):1799-813
Date
Dec-2005
Language
English
Publication Type
Article
Keywords
Adoptive Transfer
Animals
CD4-Positive T-Lymphocytes - immunology
Cyclosporine - pharmacology
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Eruptions - immunology - pathology
Female
Nevirapine - antagonists & inhibitors - metabolism - toxicity
Rats
Rats, Inbred BN
Spleen - cytology - drug effects - immunology
T-Lymphocyte Subsets - immunology
Tacrolimus - pharmacology
Abstract
Previously, we reported a new animal model of an idiosyncratic drug reaction in which nevirapine causes a skin rash in some rats that has characteristics similar to the reaction that occurs in humans. Strong evidence that the reaction is immune-mediated was found; specifically, low-dose pretreatment induced tolerance, while with rechallenge, the time to onset decreased and the severity increased. Furthermore, splenocytes from rechallenged rats transferred rash susceptibility to na?ve recipients. We now report the results of studies to explore the immune aspects of this reaction. T cells were found to play an important role, as demonstrated by their ability to adoptively transfer susceptibility to the skin reaction. Of these T cells, CD4+ cells are the likely effectors because they were capable of transferring susceptibility and the reaction was delayed in rats partially depleted of CD4+ T cells. In contrast, it appears that CD8+ T cells are not essential, as CD8+ T cells were unable to transfer sensitivity to a na?ve animal and rats depleted of CD8+ T cells still developed skin rash. Unlike the penicillamine model, where we have demonstrated that the tolerance induced by low-dose treatment is immune-mediated, tolerance induced by low-dose nevirapine appears to be largely due to induction of metabolism as it can be overcome by inhibition of cytochrome P450. Pretreatment with the immunosuppressants, cyclosporine and tacrolimus, prevented the rash and even led to resolution of the rash during nevirapine treatment. These studies reinforce the hypothesis that the reaction in this model is similar to that which occurs in humans. In particular, the finding that CD4+ T cells may play a central role in this model fits with the observation that the incidence of idiosyncratic reactions to nevirapine in humans appears to be lower in patients with low CD4+ counts.
PubMed ID
16359170 View in PubMed
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IgA rheumatoid factor correlates with changes in B and T lymphocyte subsets and disease manifestations in rheumatoid arthritis.

https://arctichealth.org/en/permalink/ahliterature14264
Source
J Rheumatol. 1997 Feb;24(2):269-74
Publication Type
Article
Date
Feb-1997
Author
S. Arinbjarnarson
T. Jonsson
K. Steinsson
A. Sigfusson
H. Jonsson
A. Geirsson
J. Thorsteinsson
H. Valdimarsson
Author Affiliation
Department of Immunology, National University Hospital, Reykjavík, Iceland.
Source
J Rheumatol. 1997 Feb;24(2):269-74
Date
Feb-1997
Language
English
Publication Type
Article
Keywords
Adult
Aged
Antigens, CD - immunology
Arthritis, Rheumatoid - etiology - immunology
B-Lymphocyte Subsets - immunology
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - immunology
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Humans
Immunoglobulin A - analysis
Immunoglobulin Isotypes - analysis
Male
Middle Aged
Research Support, Non-U.S. Gov't
Rheumatoid Factor - immunology
T-Lymphocyte Subsets - immunology
Abstract
OBJECTIVE: To analyze the relationship between lymphocyte subsets, different rheumatoid factor (RF) isotypes, and clinical features in patients with rheumatoid arthritis (RA). METHODS: Patients with established RA (n = 95) were examined clinically and blood samples were collected for measurements of RF by ELISA and for analysis of lymphocyte subsets by flow cytometry. RESULTS: IgA RF positive patients had more severe disease and higher prevalence of extraarticular manifestations than the other patients. Patients with elevated IgA RF had a higher percentage of CD5+ B cells and of CD4+CD45RO+ T cells compared to the other patients with RA or controls. High percentage of CD4+CD45RO+ T cells was also significantly associated with extraarticular manifestations. Patients with the sicca syndrome had significantly higher ratio of CD5+ B cells than patients without or with other types of extraarticular manifestations. CONCLUSION: Different disease manifestations in RA may be associated not only with certain RF isotypes and RF isotype combinations but also with changes in lymphocyte subsets in the blood. The relative increase of CD4+CD45RO+ T cells in the blood of IgA RF positive patients with RA might reflect preferential recruitment of CD8+CD45RO+ T cells to inflammatory sites.
Notes
Comment In: J Rheumatol. 1997 Nov;24(11):2262-39375896
PubMed ID
9034982 View in PubMed
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The immune risk profile is associated with age and gender: findings from three Swedish population studies of individuals 20-100 years of age.

https://arctichealth.org/en/permalink/ahliterature93387
Source
Biogerontology. 2008 Oct;9(5):299-308
Publication Type
Article
Date
Oct-2008
Author
Wikby Anders
MÃ¥nsson Ingrid A
Johansson Boo
Strindhall Jan
Nilsson Sven E
Author Affiliation
Department of Natural Science and Biomedicine, School of Health Sciences, Jönköping University, Box 1026, 551 11 Jönköping, Sweden. anders.wikby@hhj.hj.se
Source
Biogerontology. 2008 Oct;9(5):299-308
Date
Oct-2008
Language
English
Publication Type
Article
Keywords
Adult
Age Factors
Aged
Aged, 80 and over
Antigens, CD45 - immunology
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - immunology
Female
Humans
Immune System - physiology
Longitudinal Studies
Male
Middle Aged
Receptors, CCR7 - immunology
Risk factors
Sex Factors
Sweden
T-Lymphocyte Subsets - immunology
Abstract
Earlier we identified an Immune Risk Profile (IRP) of very old individuals, 86-94 years of age, characterised by an inverted CD4/CD8 ratio and associated with persistent cytomegalovirus infection and an increase in the numbers of CD3+CD8+CD28- cells. In the present study we included data from a population-based sample in the age range of 20-79 years to examine the prevalence of individuals with an inverted CD4/CD8 ratio relative to age and gender across the entire adult lifespan. Immunological monitoring that was conducted included analysis of the numbers of T-cells in the subsets CD3+, CD3+CD4+, and CD3+CD8+ as well as CD3+CD8+CD28+, CD3+CD8+CD28-, and CD8+CD45RA+CCR7+. There was found to be a significant lowering of the numbers of CD3+, CD3+CD4+, and CD3+CD8+, and of the CD8+CD45RA+CCR7+ cells across the adult life-span. Notably, the prevalence of individuals with an inverted CD4/CD8 ratio increased from about 8% in the age range of 20-59 years to about 16% in the age range of 60-94 years. The mortality rate in individuals with an inverted CD4/CD8 ratio also increased significantly above the age of 60. Interestingly, the proportion of individuals with an inverted CD4/CD8 ratio was found to be significantly higher in men, whereas the numbers of CD3+CD4+ helper and CD8+CD45RA+CCR7+ naïve cells and the CD4/CD8 ratio were found to be significantly higher in women. These results highlight the importance of functioning of the thymus in the development of IRP and may partly account for the differences between sexes in terms of longevity.
PubMed ID
18369735 View in PubMed
Less detail

Immune system changes during simulated planetary exploration on Devon Island, high arctic.

https://arctichealth.org/en/permalink/ahliterature163386
Source
BMC Immunol. 2007;8:7
Publication Type
Article
Date
2007
Author
Brian Crucian
Pascal Lee
Raymond Stowe
Jeff Jones
Rainer Effenhauser
Raymond Widen
Clarence Sams
Author Affiliation
Wyle Laboratories/NASA-JSC, Houston, Texas 77058, USA. bcrucian@ems.jsc.nasa.gov
Source
BMC Immunol. 2007;8:7
Date
2007
Language
English
Publication Type
Article
Keywords
Arctic Regions
Biological Markers - blood
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - immunology
Canada
Cells, Cultured
Cytokines - analysis - blood - immunology
DNA, Viral - blood
Geography
Herpesvirus 4, Human - physiology
Humans
Hydrocortisone - blood
Immune System - physiology
Immunoglobulin G - blood
Immunoglobulin M - blood
Immunophenotyping
Male
Reproducibility of Results
Space Flight
Space Simulation
Stress, Physiological
T-Lymphocyte Subsets - immunology
T-Lymphocytes - immunology
Time Factors
Viral Load
Virus Latency
Abstract
Dysregulation of the immune system has been shown to occur during spaceflight, although the detailed nature of the phenomenon and the clinical risks for exploration class missions have yet to be established. Also, the growing clinical significance of immune system evaluation combined with epidemic infectious disease rates in third world countries provides a strong rationale for the development of field-compatible clinical immunology techniques and equipment. In July 2002 NASA performed a comprehensive immune assessment on field team members participating in the Haughton-Mars Project (HMP) on Devon Island in the high Canadian Arctic. The purpose of the study was to evaluate the effect of mission-associated stressors on the human immune system. To perform the study, the development of techniques for processing immune samples in remote field locations was required. Ten HMP-2002 participants volunteered for the study. A field protocol was developed at NASA-JSC for performing sample collection, blood staining/processing for immunophenotype analysis, whole-blood mitogenic culture for functional assessments and cell-sample preservation on-location at Devon Island. Specific assays included peripheral leukocyte distribution; constitutively activated T cells, intracellular cytokine profiles, plasma cortisol and EBV viral antibody levels. Study timepoints were 30 days prior to mission start, mid-mission and 60 days after mission completion.
The protocol developed for immune sample processing in remote field locations functioned properly. Samples were processed on Devon Island, and stabilized for subsequent analysis at the Johnson Space Center in Houston. The data indicated that some phenotype, immune function and stress hormone changes occurred in the HMP field participants that were largely distinct from pre-mission baseline and post-mission recovery data. These immune changes appear similar to those observed in astronauts following spaceflight.
The immune system changes described during the HMP field deployment validate the use of the HMP as a ground-based spaceflight/planetary exploration analog for some aspects of human physiology. The sample processing protocol developed for this study may have applications for immune studies in remote terrestrial field locations. Elements of this protocol could possibly be adapted for future in-flight immunology studies conducted during space missions.
Notes
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PubMed ID
17521440 View in PubMed
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Increased chemiluminescence of whole blood and normal T-lymphocyte subsets in severe nodular acne and acne fulminans.

https://arctichealth.org/en/permalink/ahliterature73101
Source
Acta Derm Venereol. 1995 Jan;75(1):1-5
Publication Type
Article
Date
Jan-1995
Author
S L Karvonen
L. Räsänen
E. Soppi
H. Hyöty
M. Lehtinen
T. Reunala
Author Affiliation
Department of Dermatology, University Hospital of Oulu, Finland.
Source
Acta Derm Venereol. 1995 Jan;75(1):1-5
Date
Jan-1995
Language
English
Publication Type
Article
Keywords
Acne Vulgaris - blood - drug therapy - immunology
Adolescent
Adult
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - immunology
Chemiluminescent Measurements
Comparative Study
Female
HLA-C Antigens - analysis
HLA-DR Antigens - analysis
Humans
Killer Cells, Natural - immunology
Luminol - diagnostic use
Male
Neutrophils - immunology
Receptors, IgG - analysis
Receptors, Interleukin-2 - analysis
Remission Induction
T-Lymphocyte Subsets - immunology
T-Lymphocytes, Helper-Inducer - immunology
T-Lymphocytes, Regulatory - immunology
Abstract
To investigate the inflammatory and immunological aspects of severe acne, we examined the luminol-enhanced chemiluminescence of whole blood, T-cell subsets and natural killer cell functions in 11 patients with severe nodular acne and 4 patients with acne fulminans. In patients with severe nodular acne, the active phase of the disease, compared to the values in remission (means 47 mV, SD 24.8 and 32 mV, SD 8.3, p
PubMed ID
7747527 View in PubMed
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Nearly identical T-cell receptor V-gene usage at birth in two cohorts of distinctly different ethnic origin: influence of environment in the final maturation in the adult.

https://arctichealth.org/en/permalink/ahliterature223550
Source
Scand J Immunol. 1992 Jul;36(1):71-8
Publication Type
Article
Date
Jul-1992
Author
N S Ramakrishnan
J. Grunewald
C H Janson
H. Wigzell
Author Affiliation
Department of Immunology, Karolinska Institute, Stockholm, Sweden.
Source
Scand J Immunol. 1992 Jul;36(1):71-8
Date
Jul-1992
Language
English
Publication Type
Article
Keywords
Age Factors
Antibodies, Monoclonal
Asia - ethnology
CD4-Positive T-Lymphocytes - immunology
Gene Frequency
Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
Genes
Humans
Infant, Newborn
Receptors, Antigen, T-Cell, alpha-beta - genetics
Scandinavia - ethnology
T-Lymphocyte Subsets - immunology
Abstract
We have previously analysed the T-cell receptor (TCR) V-gene usage in peripheral blood T lymphocytes from a group of healthy Scandinavians, and described a biased representation (i.e. a statistically significant higher median representation) for some of the TCR V genes towards the CD4+ subpopulation. In a subsequent study the usage of the same V genes was analysed in single positive (CD4+ CD8- and CD4- CD8+) human thymocytes, and a similar type of skewness was noted. These observations might be explained by an influence of the specificity of the TCR of thymocytes on the maturation into the CD4+ or the CD8+ lineage. Such a model would assume an interaction between a common determinant on the major histocompatibility complex (MHC) class I or class II molecules, or with a peptide that is preferentially presented by either of the two molecules, and the TCR on the maturing thymocyte. To investigate the possible influence of a different genetic background and environment on skewed TCR V-gene representation, we have in this study analysed the TCR V-gene usage in peripheral blood and umbilical cord blood lymphocytes obtained from Asians, with a different ethnic and environmental background from our previous Scandinavian subjects. In the umbilical cord blood lymphocytes the TCR V-gene usage was close to identical between the two different ethnic groups in both CD4+ and CD8+ subpopulations. Analysing the peripheral blood lymphocyte (PBL) TCR V-gene usage, we found that three of the four monoclonal antibodies (MoAb) with a biased reactivity towards the CD4+ subpopulation in the Scandinavian group also showed a similar skewed reactivity in this study. Thus, the majority of the TCR V genes were used in a similar way. Some minor but definite discrepancies could be detected when comparing TCR V-gene usage in adult individuals from these two different ethnic groups. These differences could be inferred to be due to selective peripheral expansion through environmental pressure of T cells utilizing a specific V beta gene segment. We conclude that a striking preservation of biased TCR V-gene usage does exist in humans of distinctly different ethnic origin.
PubMed ID
1352064 View in PubMed
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Ricin enhances IgE responses by inhibiting a subpopulation of early-activated IgE regulatory CD8+ T cells.

https://arctichealth.org/en/permalink/ahliterature57727
Source
Immunology. 1993 Feb;78(2):226-36
Publication Type
Article
Date
Feb-1993
Author
D. Diaz-Sanchez
T H Lee
D M Kemeny
Author Affiliation
Department of Allergy and Allied Respiratory Disorders, United Medical School of Guy's Hospital, London.
Source
Immunology. 1993 Feb;78(2):226-36
Date
Feb-1993
Language
English
Publication Type
Article
Keywords
Animals
Antigens, CD8 - analysis
CD4-Positive T-Lymphocytes - immunology
Immunoglobulin E - biosynthesis
Leukocyte Count
Phospholipases A - immunology
Rats
Rats, Inbred Strains
Research Support, Non-U.S. Gov't
Ricin - immunology
Spleen - immunology
T-Lymphocyte Subsets - immunology
T-Lymphocytes, Regulatory - immunology
Abstract
Ricin, a toxic lectin from castor beans greatly enhances IgE responses to bee venom phospholipase A2 (PLA2) in high and low IgE responder strains of rat. The increase in IgE is accompanied by a 60% reduction in the number of CD8+ but not CD4+ T cells in the spleen. Optimal enhancement of IgE by ricin occurs when it is given at the same time as the antigen or 24 hr later, suggesting that it acts on cells which were activated as a consequence of immunization. Radio ligand-binding studies with 125I ricin were used to compare the number of ricin binding sites on CD4+ and CD8+ T cells. No difference was seen in either the affinity or the number of receptors for ricin on the CD4+ and CD8+ T cells of unimmunized rats. In contrast, CD8+ T cells taken from rats which had been immunized with 10 micrograms of PLA2 24 hr earlier demonstrated considerably more ricin receptors (3.9 x 10(7) +/- 2.2 x 10(6) binding sites/cell) than CD4+ T cells (3.19 x 10(6) +/- 1.08 x 10(6) binding sites/cell). However the affinity of the receptors for ricin was unchanged. Cytofluorographic analysis with fluorescein isothiocyanate (FITC)-labelled ricin confirmed these observations and indicated that increased ricin binding occurred on a subpopulation of CD8+ T cells. The effect of CD8+ T cells on IgE regulation was investigated by adoptive transfer. 1 x 10(8) highly purified (> 98%) splenic CD8+ T cells collected from Brown Norway rats 3 days after immunization with 10 micrograms of PLA2 were adoptively transferred to naive, syngeneic recipients. The IgE antibody response to PLA2 + A1(OH)3 seen in these animals was reduced by 91%. Adoptive transfer of CD4+ T cells from the same donor animals did not induce suppression and nor did adoptive transfer of CD8+ T cells from animals given both ricin and PLA2. However, when recipients of CD8+ T cells taken from rats immunized with PLA2 were immunized with a different antigen [ovalbumin (OVA)] and A1(OH)3 the IgE antibody response was also suppressed, although to a lesser extent (66%). These results show that co-administration of ricin and PLA2 depletes a subpopulation of ricin-sensitive, early activated CD8+ T cells and that these CD8+ T cells are potent suppressors of the primary IgE response.
PubMed ID
8097181 View in PubMed
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Transfer of allergic airway responses with antigen-primed CD4+ but not CD8+ T cells in brown Norway rats.

https://arctichealth.org/en/permalink/ahliterature57669
Source
J Clin Invest. 1995 Sep;96(3):1303-10
Publication Type
Article
Date
Sep-1995
Author
A. Watanabe
H. Mishima
P M Renzi
L J Xu
Q. Hamid
J G Martin
Author Affiliation
Meakins-Christie Laboratories, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
Source
J Clin Invest. 1995 Sep;96(3):1303-10
Date
Sep-1995
Language
English
Publication Type
Article
Keywords
Allergens - immunology
Animals
Bronchoalveolar Lavage Fluid - cytology
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - immunology
Comparative Study
Eosinophils - cytology - immunology
Hypersensitivity - immunology
Immunity, Cellular
Immunoglobulin E - analysis
Immunotherapy, Adoptive
Inflammation
Leukocyte Count
Lung - immunology
Lymph Nodes - immunology
Lymphocyte Activation
Lymphocyte Transfusion
Male
Ovalbumin - immunology
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Respiratory System - immunology
Serum Albumin, Bovine - immunology
Skin Tests
T-Lymphocyte Subsets - immunology
Abstract
Activated CD4+ helper T cells have been demonstrated in asthmatic airways and postulated to play a central role in eliciting allergic inflammation; direct evidence of their involvement seems to be lacking. We hypothesized that CD4+ T cells have the potential to induce allergic responses to antigen challenge, and tested this hypothesis in a model of allergic bronchoconstriction, the Brown Norway rat, using the approach of adoptive transfer. Animals were actively sensitized to either ovalbumin (OVA) or BSA and were used as donors of T cells. W3/25(CD4)+ or OX8(CD8)+ T cells were isolated from the cervical lymph nodes of sensitized donors and transferred to naive BN rats. 2 d after adoptive transfer recipient rats were challenged by OVA inhalation, and changes in lung resistance (RL), bronchoalveolar lavage (BAL) cells, and serum levels of antigen-specific IgE were studied. After OVA challenge recipients of OVA-primed W3/25+ T cells exhibited sustained increases in RL throughout the entire 8-h observation period and had significant bronchoalveolar lavage eosinophilia, which was detected by immunocytochemistry using an antimajor basic protein mAb. Recipients of BSA-primed W3/25+ T cells or OVA-primed OX8+ T cells failed to respond to inhaled OVA. OVA-specific immunoglobulin E was undetectable by ELISA or skin testing in any of the recipient rats after adoptive transfer. In conclusion, antigen-induced airway bronchoconstriction and eosinophilia were successfully transferred by antigen-specific W3/25+ T cells in Brown Norway rats. These responses were dependent on antigen-primed W3/25+ T cells and appeared to be independent of IgE-mediated mast cell activation. This study provides clear evidence for T cell mediated immune mechanisms in allergic airway responses in this experimental model.
PubMed ID
7657805 View in PubMed
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