Relationship between IL-2 receptor expression and proliferative responses in lymphocytes from HIV-1 seropositive homosexual men

Chopra, Rajesh; Raj, Nitin; Scally, John P.; Donnenberg, A. D.; Adler, William H.; Saah, A. J.; Margolick, Joseph B.

doi:10.1111/j.1365-2249.1993.tb03347.x

Cited by 11 publications

(2 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data suggest that cellular factors other than IL-2 secretion may regulate a CD8 T cells ability to proliferate. Differences in IL-2 receptor expression or signaling may be a better phenotypic representation of HIV-1-specific CD8 T cells capable of proliferation and would explain the differences seen in recent studies and in the present study which indicates compromised proliferative capacity in primary HIV infection 36 .…”

Section: Discussionmentioning

confidence: 45%

CD8 T-Cell Proliferative Capacity Is Compromised in Primary HIV-1 Infection

Heath

Sabbaj²,

Bansal³

et al. 2011

JAIDS Journal of Acquired Immune Deficiency Syndromes

View full text Add to dashboard Cite

Understanding the correlates of immunity that control HIV-1 infection is imperative to our understanding of HIV-1 disease and vaccine development. HIV-1 specific cytotoxic T lymphocytes (CTL) are fundamental to the control of viremia, however which T cell repertoire components enact this control remains unclear. We hypothesize that polyfunctional HIV-1-specific CD8 T cells capable of viral control are present in most patients early in infection and these cells are distinguished by their ability to secrete IL-2 and proliferate. We examined HIV-1-specific CD8 T cell proliferation and cytokine secretion in primary HIV-1 infection (PHI) using known HIV-1 CTL epitopes to exclude CD4 bystander effect. We found that only a subset of PHI patients demonstrated “CD4 independent” CD8 proliferation ex vivo. The remainder of the patients lacked HIV-1-specific CD8 T cells with proliferative capacity, even after the addition of exogenous IL-2. Amongst the proliferators, IL-2 production from the total HIV specific CD8 T cell population correlated with proliferation. Surprisingly though, we did not routinely detect both IL-2 secretion and proliferative capacity from the same antigen specific CD8 T cells. Thus there are distinct and heterogeneous populations of CD8 T cells- phenotypically characterized by either proliferation, or IL-2 secretion, and few with dual capacity. Generation of these responses may be an important measure of HIV-1 control but are not universal following PHI. Furthermore, the heterogeneity of this population suggests that a simple measure of an effective vaccine response remains elusive.

show abstract

Section: Discussionmentioning

confidence: 45%

CD8 T-Cell Proliferative Capacity Is Compromised in Primary HIV-1 Infection

Heath

Sabbaj²,

Bansal³

et al. 2011

JAIDS Journal of Acquired Immune Deficiency Syndromes

View full text Add to dashboard Cite

show abstract

“…CD4 ϩ T cells from HIV-infected patients are defective in granulysin expression after IL-2 stimulation (5). Most of the evidence in HIV infection indicates that constitutive expression of IL-2R␣/␤/␥ on CD4 ϩ T cells is similar to healthy adults (53)(54)(55). The present studies show that CD4 ϩ T cells from HIV-infected patients stimulated with IL-2 failed to induce the expression of IL-2R␤ and to activate both Akt and STAT5.…”

Section: Discussionmentioning

confidence: 57%

Late Expression of Granulysin by Microbicidal CD4+ T Cells Requires PI3K- and STAT5-Dependent Expression of IL-2Rβ That Is Defective in HIV-Infected Patients

Zheng

Jones²,

Shi³

et al. 2008

The Journal of Immunology

View full text Add to dashboard Cite

Granulysin is a cytolytic effector molecule used by lymphocytes to kill tumor and microbial cells. Regulation of granulysin production is complex. A significant delay (5 days) following stimulation of CD4+ T cells with IL-2 occurs before granulysin is produced. Unfortunately, the mechanisms responsible for this delay are unknown. We have recently demonstrated that granulysin-mediated killing of Cryptococcus neoformans by CD4+ T cells is defective during HIV infection. This is because CD4+ T cells from HIV-infected patients fail to produce granulysin in response to IL-2 activation. The present studies examined the mechanism of delayed production of granulysin and the mechanism of the defect in HIV patients. We demonstrate that IL-2 initially requires both STAT5 and PI3K activation to increase expression of IL-2Rβ, produce granulysin, and kill C. neoformans. The increased expression of IL-2Rβ precedes granulysin, and preventing the increased expression of IL-2Rβ using small interfering RNA knockdown abrogates granulysin expression. Moreover, following the increased expression of IL-2Rβ, blocking subsequent signaling by IL-2 using IL-2Rβ-specific blocking Abs abrogates expression of granulysin. Finally, CD4+ T cells from HIV-infected patients, who are defective in both STAT5 and PI3K signaling, fail to express IL-2Rβ and fail to produce granulysin. These results suggest that IL-2 signals via PI3K and STAT5 to increase expression of IL-2Rβ, which in turn is required for production of granulysin. These results provide a mechanism to explain the “late” production of granulysin during normal T cell responses, as well as for defective granulysin production by CD4+ T cells in HIV-infected patients.

show abstract

Dysregulation of the interleukin-2 receptor ?- and ?-chain expression in CD4 and CD8 T cells in HIV infection

Johnson

Parkin

1997

Cytometry

View full text Add to dashboard Cite

Peripheral blood mononuclear cells were prepared from human immunodeficiency virus‐positive (HIV+) individuals (n = 46) to investigate the expression of both chains of the interleukin‐2 receptor. Both qualitative and quantitative changes in expression were observed. Total lymphocyte expression of the IL‐2α chain (CD25) was decreased compared with HIV‐negative (HIV−) controls. This was due to the decrease in the CD4+ population, which favored expression of this receptor, rather than a decrease in expression, per se. CD8+ lymphocytes expressed the β chain (CD122) in the absence of the α chain. However, a significant increase in the number of peripheral blood CD8+ lymphocytes expressing mainly the β subunit was observed in HIV+ patients (P = 0.02). This was observed to a similar extent in asymptomatic and symptomatic patients and characterized a subpopulation of T lymphocytes expressing high levels of CD8. Lymphocytes from patients with advanced HIV disease failed to up‐regulate both α and β chains in response to mitogenic concentrations of phytohaemagglutanin. However, those cells that were able to up‐regulate both of the IL‐2 receptors were capable of effective signal transduction through the receptor, increasing the proliferative response to stimulation. Cytometry 30:289–295, 1997. © 1998 Wiley‐Liss, Inc.

show abstract

Relationship between IL-2 receptor expression and proliferative responses in lymphocytes from HIV-1 seropositive homosexual men

Cited by 11 publications

References 38 publications

CD8 T-Cell Proliferative Capacity Is Compromised in Primary HIV-1 Infection

CD8 T-Cell Proliferative Capacity Is Compromised in Primary HIV-1 Infection

Late Expression of Granulysin by Microbicidal CD4+ T Cells Requires PI3K- and STAT5-Dependent Expression of IL-2Rβ That Is Defective in HIV-Infected Patients

Dysregulation of the interleukin-2 receptor ?- and ?-chain expression in CD4 and CD8 T cells in HIV infection

Contact Info

Product

Resources

About