Studies on the roles of T helper type I and type II cytokines in HIV immunopathogenesis:
نام عام مواد
[Thesis]
نام نخستين پديدآور
M. P. Daftarian
عنوان اصلي به قلم نويسنده ديگر
Role and regulation of interleukin-10
نام ساير پديدآوران
F. K. Diaz-Mitoma, A.
وضعیت نشر و پخش و غیره
نام ناشر، پخش کننده و غيره
University of Ottawa (Canada)
تاریخ نشرو بخش و غیره
1997
مشخصات ظاهری
نام خاص و کميت اثر
158
یادداشتهای مربوط به پایان نامه ها
جزئيات پايان نامه و نوع درجه آن
Ph.D.
کسي که مدرک را اعطا کرده
University of Ottawa (Canada)
امتياز متن
1997
یادداشتهای مربوط به خلاصه یا چکیده
متن يادداشت
Infection of immune cells with human immunodeficiency virus (HIV) induces dysregulation of cytokines which may play a vital role in HIV pathogenesis. I analyzed the expression of Th1 (interferon-usd\gamma,usd (IFN-usd\gamma)\rbrackusd and Th2 (interleukin-4 (IL-4), IL-10) type cytokines in unstimulated and mitogen stimulated peripheral blood mononuclear cells (PBMC) from HIV seropositive (HIV patients. It was determined that IFN-usd\gammausd mRNA in unstimulated PBMC was significantly decreased and IL-10 mRNA as well as IL-10 protein was significantly increased in patients with <400 CD4 T cells/mm (n = 30) as compared to patients with >400 CD4 T cells/mm (n = 6) and normal controls (n = 16). Mitogen stimulation of PBMC revealed two groups of HIV low and normal IL-10 producers. Production of IL-4 was reduced in HIV individuals with <400 CD4 T cells/mm while it was comparable to that of HIV controls in those with >400 CD4 T cells/mm However, ability to produce IFN-y by mitogen stimulated PBMC and CD4 T cells was not impaired in HIV individuals. These results suggest that PBMC of HIV exhibit dysregulation of Th2 type cytokines which may play a role in HIV immunopathogenesis. In the next set of experiments, the IL-10 production was correlated with the levels of proliferative responses to recall antigens. Low IL-10 producers proliferated in response to recall antigens, and demonstrated enhanced recall antigen-induced proliferation upon addition of anti-IL-10 antibodies and/or IL-12. Conversely, normal IL-10 producers had PBMC that failed to proliferate to recall antigens, and did not demonstrate enhanced recall antigen-induced proliferation upon addition of anti-IL-10 antibodies and/or IL-12. Source of the IL-10 production in PBMC of HIV individuals was shown to be monocytes, while, in HIV controls, it was produced by both T cells and monocytes. The molecular mechanisms underlying the production of IL-10 are not clear. I have demonstrated that monocytes/macrophages are required for IL-10 production by normal activated T cells. IL-10 production was significantly downregulated in both T cell and monocyte depleted PBMC compared to undepleted PBMC, and IL-10 production could be restored following addition of monocyte conditioned medium (MCM), this suggested that IL-10 production by T cells is regulated by monokine(s) produced by activated monocytes. The monokine(s) responsible for IL-10 induction by T cells were further studied. Addition of IL-6 and IL-12 enhanced IL-10 production in monocyte depleted PBMC in a dose dependent and additive manner. With respect to regulation of IL-10 produced by monocytes, tumor necrosis factor usd\alphausd (TNF-usd\alpha)usd was found to induce IL-10 production by resting purified monocytes. Taken together, these findings suggest that IL-10 production by human T cells and monocytes is differentially regulated. IL-12 and IL-6 induce the expression of IL-10 by PHA stimulated T cells whereas TNF-usd\alphausd induces IL-10 production by monocytes. Since IL-10 inhibits production of IL-6, IL-12 and TNF-usd\alpha,usd these results may indicate a potential mechanism of negative feedback regulation of the immune system. Furthermore, mitogen stimulated PBMC from HIV individuals produced significantly lower levels of IL-12 than did those from HIV-controls. A defect in IL-12 induction may partially cause IL-10 dysregulation in HIV infection.
موضوع (اسم عام یاعبارت اسمی عام)
موضوع مستند نشده
Health and environmental sciences
موضوع مستند نشده
Immune deficiency
موضوع مستند نشده
Immunology
نام شخص به منزله سر شناسه - (مسئولیت معنوی درجه اول )