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.
T lymphocytes may play a regulatory role in the development of allergic airway hyperresponsiveness (AHR). We have studied the relationship between airway responsiveness and a number of immunological changes in Brown-Norway rats sensitized intraperitoneally and repeatedly exposed to ovalbumin (OVA) aerosol. Acetylcholine provocation concentration (PC)150 (the concentration of acetylcholine causing a 150% increase of base-line lung resistance) was measured and peripheral blood and bronchoalveolar lavage (BAL) cells were collected 18-24hr after the final exposure. Total and OVA-specific IgE in serum was measured by enzyme-linked immunosorbent assay (ELISA). Mononuclear cells were analysed by flow cytometry after labelling with monoclonal antibodies against CD2 (pan T-cell marker), CD4, CD8 (T-cell subsets) or CD25 (interleukin-2 receptor). There were significant differences in PC150 (P
Alefacept is a new biotechnology product designed for the treatment of patients with chronic plaque-type psoriasis who have disease severe enough to make them eligible for phototherapy or systemic therapy. In two randomized controlled phase III trials of patients with moderate-to-severe disease, alefacept showed a modest but statistically significant increase in the number of responders compared to placebo. Alefacept's dose-dependent CD4+ T lymphocyte-depleting effect requires monitoring; however, no association has been found between this adverse effect and serious adverse events, particularly infection. Due to lack of direct comparative data, it is difficult to predict exactly how alefacept will fit into the current rotational psoriasis therapy paradigm.
The effect of immunotherapy (IT) on T-cell subsets in peripheral blood and bronchoalveolar lavage fluid (BAL) was examined in 15 patients with rhinoconjunctivitis and asthma caused by sensitivity to birch pollen. They were treated with IT for 3 years. Seven patients were treated with highly standardized birch-pollen extract (Pharmacia, Sweden). Eight untreated patients served as controls. Histamine challenge, blood sampling, and BAL were performed before (January, February), and at the peak of, the birch-pollen season (May). The subpopulations of T cells in peripheral blood and BAL fluid were investigated by immunocytochemistry and flow cytometry. During the birch-pollen season, the percentage of CD3+ and CD4+ cells of blood mononuclear cells in the IT patients increased significantly (P
The influence of polarized polychromatic light on immunocompetent cells in complex with immunomodulated bronchomunal is studied. Data of content of the main cytokines taking part in development of inflammation are presented. It is cleared up that polarized light increases the number of T-lymphocyties, normalizes ratio of subpopulation of T-lymphocyties and level of serum FNO-alpha and level of interleukin-4 reaches the level of healthy people. It is ascertained that complex use bronchomunal and polarized polychromatic increases level of serum interferon-gamma.
BACKGROUND: Gamma-delta (gammadelta) T cells regulate immune responses to foreign protein at mucosal surfaces. Whether they can modify allergen-induced early (EAR) and late airway responses (LAR) is unknown. OBJECTIVE: We have tested the hypothesis that the CD8+ subtype of gammadelta T cells decreases allergen-induced LAR and airway eosinophilia in the rat. METHODS: Brown Norway rats were administered, intraperitoneally, 3.5 x 10(4) lymph node CD8+gammadelta T cells from naive or sensitized rats. The recipients were sensitized to ovalbumin (OVA) in Al(OH)(3) 3 days after cell transfer and challenged with aerosolized OVA 14 days later. Serum IgE was measured before allergen challenge. After challenge, lung resistance was monitored for 8 hours and then bronchoalveolar lavage (BAL) was analyzed for eosinophil major basic protein (MBP), IL-4, IL-5, IL-13, and IFN-gamma messenger RNA-expressing cells. RESULTS: gammadelta T cells from naive donors significantly decreased LAR in OVA-challenged sensitized rats, whereas MBP(+) eosinophils were decreased by both gammadelta T cells from naive and sensitized donors. EAR and serum IgE levels were unchanged. The expression of IL-4, IL-5, and IL-13 by BAL cells of gammadelta T cell recipients was attenuated compared with OVA-challenged controls. This was accompanied by an increase in the expression of IFN-gamma. CONCLUSIONS: Our results are consistent with a suppressive role of CD8+gammadelta T cells on allergic airway responses. However, only gammadelta T cells from naive donors inhibit LAR.
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.
A family with three cases of macroglobulinaemia of undetermined significance (MGUS), and one case each of immunoblastic lymphoma, Waldentr?m's macroglobulinaemia and multiple myeloma was first described 20 years ago. We have previously identified 10 out of 35 healthy family members tested whose lymphocytes produced abnormally high amounts of immunoglobulins in culture. In the present study lymphocyte subpopulations of these hyper-responders have been further characterized and lymphocyte reactivity and survival in vitro have been studied. No differences were detected in the proportions of resting B lymphocytes (CD19+) co-expressing CD5, CD10, CD11b, or CD38, and the CD4/CD8 ratio of T cells was normal before and after stimulation with pokeweed mitogen (PWM). The initial rate of response in terms of immunoglobulin production was not increased, but immunoglobulin levels continued to rise during the second week of culture whereas the production peaked at 8 days in control cultures. This was associated with significantly greater survival of lymphocytes and at 14 days surviving B cells could only be identified in samples from hyper-responders. A lymph node removed because of tuberculosis from a family member 23 years before the diagnosis of multiple myeloma showed very marked Bcl-2 expression in a B cell follicle. This was not seen in a tuberculous lymph node from an unrelated subject. Stimulated cultures from three hyper-responders tested demonstrated significantly higher retention of Bcl-2 in B cells compared with one family control and six unrelated controls. We conclude that the increased production of immunoglobulins previously observed in this family with an inherited tendency for benign and malignant B cell proliferation is the result of enhanced B cell survival, which is associated with increased expression of Bcl-2 following stimulation.
AIM: Recently, we reported typical endoscopic findings and an increment in gammadelta+ T cells in the foregut among children with food-sensitive enteropathy other than coeliac disease. To find out the extend to which the upregulation of the local immune response might explain gastrointestinal (GI) complaints of the foregut, we sought to examine by the increment in gammadelta+ T cells a I-y consecutive series of children referred for recurrent GI complaints to a tertiary-level hospital. METHODS: A 1-y cohort of 102 children scheduled for gastroduodenoscopy were examined for mucosal histology and the densities of CD3+, alphabeta+ and alphabeta+ T-cell subsets from mid-duodenal specimens. The final diagnostic categories were used in analysing the data. RESULTS: Fifteen subjects showed villous atrophy and a high gammadelta+ T-cell density; the finding being compatible with coeliac disease (CD). At the other extreme, 20 subjects in whom diagnostic GI diseases were ruled out showed low densities and served as controls. The subjects reporting GI symptoms after an open food challenge with milk and/or cereals (n = 18) as well as children remitting with a milk- or cereal-eliminating diet but not responding to a challenge (n = 23) also expressed significantly higher densities of gammadelta+ T cells than the controls. In all, 45 of 102 children could be considered to have an elevated gamma6+ T-cell density as an indication of locally activated immune response. Lack of villous architecture and lymphonodular hyperplasia of the duodenal bulb as an endoscopic finding and atopic dermatitis but not the presence of DQ2 alleles showed a close association with these increased densities. CONCLUSION: Considering that an elevated incidence of gammadelta+ T cells is an indication of mucosal response against luminal antigens, up to half the children with prolonged GI symptoms have immune mediated disorder; CD and food allergy being the most obvious clinical entities.
The authors tested an alternative method for CD4 and CD8 T lymphocytes enumeration, the immunoalkaline phosphatase method (IA), in three African countries and in Denmark. The IA determinations from 136 HIV antibody positive and 105 HIV antibody negative individuals were compared to the corresponding results obtained by flow cytometry (FC) performed in the respective countries. The authors found good correspondence between the two methods for measurements of CD4 and CD8 T lymphocytes independent of serological status and geographical site. However, the CD4 and CD8 T lymphocytes values obtained by the two methods are not interchangeable as IA compared to FC consistently gives higher percentage of CD4 T lymphocytes, and lower percentage of CD8 T lymphocytes. Mean differences between the two methods did not differ between the three African countries indicating that the IA method provides systematic results. Replicate measurements suggested good correspondence between results obtained by IA. By using an IA level of