Glucocorticoid-induced tumor necrosis factor receptor family-related protein triggering enhances HIV-specific CD4+ T cell cytokine secretion and protects HIV-specific CD4+ T cells from apoptosis.

نویسندگان

  • Timothy P Lahey
  • Suzanne D Loisel
  • Wendy Wieland-Alter
چکیده

Human immunodeficiency virus (HIV)-specific CD4(+) T cell cytokine secretion is characteristically weak during HIV infection, in part because HIV-specific CD4(+) T cells undergo massive apoptotic deletion. Glucocorticoid-induced tumor necrosis factor (TNF) receptor family-related (GITR) protein triggering enhances murine antigen-specific T cell cytokine secretion by protecting T cells from apoptosis. Therefore, we investigated the impact of GITR triggering on HIV-specific CD4(+) T cell cytokine secretion and on apoptosis of HIV-specific CD4(+) T cells. In HIV-infected subjects, CD4(+) T cell surface expression of GITR was greater than that in uninfected control subjects, and phytohemagglutinin induction of additional GITR expression was impaired. However, antibody triggering of GITR significantly increased HIV-specific CD4(+) T cell expression of TNF- alpha and interferon (IFN)- gamma . The percentage increase in HIV-specific CD4(+) T cell expression of TNF- alpha correlated directly with the absolute peripheral CD4(+) T cell count. Furthermore, GITR triggering reduced the expression of intracellular activated caspase-3 in HIV-specific CD4(+) T cells. Taken together, these data suggest that, despite abnormal GITR expression during HIV infection, GITR triggering enhances HIV-specific CD4(+) T cell cytokine expression and protects HIV-specific CD4(+) T cells from apoptosis.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Fas antigen stimulation induces marked apoptosis of T lymphocytes in human immunodeficiency virus-infected individuals

Apoptosis (programmed cell death) of T lymphocytes has been proposed as a mechanism which plays an important role in the pathogenesis of human immunodeficiency virus (HIV) disease. Activation of Fas (CD95) can either result in costimulation of proliferation and cytokine production or in the induction of apoptosis of T lymphocytes. This raises the possibility that Fas is involved in the observed...

متن کامل

IL-15 enhances the function and inhibits CD95/Fas-induced apoptosis of human CD4+ and CD8+ effector-memory T cells.

Although the effect of IL-15 has been described on murine cells in vitro and in vivo, its effect on human memory CD8(+) T cells is not well characterized. We show here that IL-15 preferentially enhances the activation and effector function of human effector-memory CD45RA(-)CD62L(-) and CD45RA(+)CD62L(-) CD4(+) and CD8(+) T cells in both healthy and HIV-infected individuals. We find that IL-15 i...

متن کامل

HIV-1 binding to CD4 on CD4+CD25+ regulatory T cells enhances their suppressive function and induces them to home to, and accumulate in, peripheral and mucosal lymphoid tissues: an additional mechanism of immunosuppression.

The establishment and persistence of many chronic infections have been demonstrated to depend on restraint of the vigor of the anti-microbial immune responses by CD4+CD25+ regulatory T (Treg) cells. In HIV-infected individuals, Treg cells suppress both HIV-specific and general CD4+ and CD8+ T cell responses. Increases of CD4+CD25+ Treg cell function during viral infections might be mediated by ...

متن کامل

Increased sensitivity of T lymphocytes to tumor necrosis factor receptor 1 (TNFR1)- and TNFR2-mediated apoptosis in HIV infection: relation to expression of Bcl-2 and active caspase-8 and caspase-3.

The destruction of CD4 T cells in human immunodeficiency virus (HIV) infection is associated with activation of apoptotic programs, partly mediated by death receptors. The role of CD95L/CD95 in depletion of patients' CD4 T cells is well documented, but the possible contribution of the tumor necrosis factor/tumor necrosis factor receptor (TNF/TNFR) pathway has not been examined. In this study, w...

متن کامل

Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells

T cell stimulation via glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) can evoke effective tumor immunity. A single administration of agonistic anti-GITR monoclonal antibody (mAb) to tumor-bearing mice intravenously or directly into tumors provoked potent tumor-specific immunity and eradicated established tumors without eliciting overt autoimmune disease. A l...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • The Journal of infectious diseases

دوره 196 1  شماره 

صفحات  -

تاریخ انتشار 2007