We studied the basic indicators of immune status of healthy persons of different age groups living in the monsoon climate in the southern Far East. The analysis shows age-dependent development of immunodepressive status, combined with increasing levels of CD16, CD25 and HLA-DR in the aging organism. Climatic and anthropogenic factors effect profoundly damaging on the body, which results in the severity of disorders of the immune system in old, old age and longevity.
Administration of Glutamic Acid Decarboxylase (GAD)65 formulated in aluminium hydroxide preserved insulin secretion in a phase II trial in recent onset Type 1 Diabetes. A subsequent European phase III trial was closed at 15months after failing to reach primary endpoint, but the majority of the Swedish patients completed the 21months follow-up. We studied the frequencies and phenotype of T cells, suppressive capacity of Tregs, GAD65-induced proliferation, and frequencies of T cells with a GAD65-specific TCR in Swedes participating in the trial. Stimulation with GAD65 induced activated T cells and also cells with a suppressive phenotype. Activated GAD65-specific effector T cells were detected by tetramer staining while the frequency of GAD65-specific Treg was not affected by the treatment. Additional doses of GAD-alum increased frequencies of CD25(+)CD127(+), but had no effect on CD25(hi)CD127(lo). Our findings indicate that GAD-alum treatment primarily induced activated T cells. GAD65-specific cells were mainly of activated phenotype.
CD4+CD25+ regulatory T (Treg) cells are engaged in the maintenance of immunological self-tolerance and suppressive control of excessive immune responses to foreign antigens. Furthermore, Treg cells infiltrate tumor tissues and may impede immune surveillance against cancer and hamper the development of an effective antitumor immunity. Depletion of Treg cells in animal models has been demonstrated to provoke tumor immunity. Attenuation of Treg-mediated suppression is therefore an interesting strategy to enhance antitumor responses. We recently found that adaptive Treg cells express COX-2 and suppress responder T cells in a PGE2-cAMP-dependent manner, which can be reversed by COX-2 inhibitors or EP-receptor antagonists. The same mechanism also appeared to be operative in patients with colorectal cancer where treatment with COX-inhibitor or cAMP-antagonist enhanced antitumor immune responses to the same extent as depletion of Treg cells. This provides mechanism-based opportunities for pharmacological intervention to interfere with Treg immunosuppression. In this review we will discuss key mechanisms used by Treg cells to suppress antitumor immunity, with emphasis on the cAMP-PKA pathway. We will also highlight some of the roles of Treg cells in cancer.