5th International AIDS Society Conference on HIV Pathogenesis and Treatment Cape Town - July 19 - 22, 2009

DISSECTING T CELL RESPONSIVENESS TO γC-CYTOKINE IN HIV INFECTED SUBJECTS

IAS Conf HIV Pathog Treat 2009 Jul 19-22;5th: Abstract No. MOAA105

C. Riou ¹, N. Malatsi¹, G. De Bruyn², R.-P. Sekaly³, C.M. Gray^1
1NICD, HIV/AIDS unit, Johannesburg, South Africa, ²Chris Hani Baragwanath Hospital, PHRU, Johannesburg, South Africa, ³University of Montreal, Immunology, Montreal, Canada

BACKGROUND: γC-cytokines play a central role in controlling T cell proliferation, differentiation and survival. It is well established that HIV-specific cells are defective in their ability to produce cytokines such as IL2. However, less is known on the ability of T cells to respond to cytokines. To define if abnormal responses to immune-activation signals could lead to T cell dysfunction and inability of T cells to control HIV replication, we analyzed the phosphorylation profiles of different Tcell subsets and HIV-specific cells in response to exogenous γC-cytokines.

METHODS: In a cohort of 11 HIV infected and 11 un-infected individuals, we assessed the profile of Stat-5 phosphorylation in total and HIV-specific cells in response to a brief exposure (15 min) to sub-optimal concentrations of IL-2 (300U/ml), IL- 7 (0.2ng/ml) and IL-15 (0.5ng/ml) using 7-color-flow cytometry.

RESULTS: In both HIV-positive and HIV-negative individuals, memory T cell responsiveness to γC-cytokines significantly decreased with cell differentiation in the CD4 and CD8 compartments, where Central Memory cells (CD45RACD27+ CCR7+) display the highest responsiveness to IL-2, IL7 and IL-15 and Effector cells (CD45RA+CD27-CCR7-) the lowest. No significant differences in Stat-5 phosphorylation were observed between HIV-positive and HIV- individuals in any subsets of total CD4 or CD8 T-cells. Importantly, HIV-specific cells were characterized by a 2-fold decrease in Stat- 5 phosphorylation in response to IL-2 triggering as compared to CMV-specific cells, despite a functional IL-7 pathway.

CONCLUSIONS: Our results indicate that T cell differentiation affects γC-cytokine responsiveness where terminally differentiated cells lose their ability to respond to cytokines. In HIV-specific cells, impaired responsiveness to IL-2 could play a role in generating functionally inefficient antigen-specific cells. Thus, differentiation status and antigen specificity both appear to have a role in determining responsiveness to immune activation signals.

2009-07-22
MOAA105
Oral Abstract Session MOAA1 - Control of HIV by Cellular Immunity

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