HIV2 Specific CD4+ T Cells: Why are they preserved? A functional and phenotypic description

Lead Research Organisation: MRC Unit, The Gambia


The worldwide AIDS pandemic is largely caused by one HIV strain called HIV-1, which after a variable length of time leads to AIDS and death in most infected people. There is a second HIV strain called HIV-2, which is mostly found in West Africa. This virus behaves quite differently from HIV-1: some HIV-2-infeceted people develop AIDS just as if they had HIV-1 but others, as many as 80%, have a normal lifespan and die of old age instead. We want to see if the immune response to the virus is different in these two groups of HIV-2-infected people, which may give useful clues about how to develop an HIV vaccine. We will be looking predominantly at cells in the blood called helper lymphocytes because these cells are the main target for HIV infection. In HIV-1 infection the helper cells that recognise HIV itself are usually lost very early in infection because the virus targets them over other cells but this may not be the case in HIV-2 infection.

Technical Summary

Virus-specific CD4+ T helper lymphocytes are critical for the maintenance of effective immunity in a number of chronic viral infections, but are characteristically undetectable in chronic HIV-1 infection except in a minority of individuals usually characterized as long-term non-progressors. Recently an explanation for this lack of virus-specific CD4+ T cell activity has been suggested by the discovery that HIV-1 preferentially targets and infects HIV-1 specific memory CD4+ T cells, thus deleting the population of cells best capable of generating a concerted immune response against the virus. Preliminary data from our ongoing studies in the Gambia suggest that HIV-specific CD4+ T cells responses may be preserved in asymptomatic individuals infected with HIV-2 and further studies are needed to confirm these observations and to more fully characterize the cellular immune response to HIV-2 infection. We hypothesize that the preservation of HIV-2 specific CD4+ T cells responses in asymptomatic HIV-2 infection may be attributable to the lack of preferential infection of HIV-2 specific CD4+ T cells by the virus. We hypothesize that either HIV-2 virions do not activate or infect dendritic cells as effectively as HIV-1 or that HIV-2-infected dendritic cells do not efficiently transfer virus to HIV-2-specific CD4+ T cells ultimately leading to a scenario in which HIV-2-specific CD4+ T cells, unlike those in HIV-1 infection, are becoming stimulated but are not becoming preferentially infected by the virus. We propose a follow-up panel of studies to compliment our ongoing studies of cellular immune responses in HIV-1 and HIV-2 infected individuals in the Fajara cohort. The aims of this study are to characterize key immunological parameters in HIV-2 infected donors stratified by CD4 count as follows:Fully characterize the functional (cytokine profiles) and phenotypic (maturation, differentiation, and activation markers) profile of HIV-2 specific CD4+ T cells using multiparameter flow cytometry (follow-on from SCC 880). Investigate whether HIV-2 specific CD4+ T cells are preferentially infected by the virus as compared to other memory CD4+ T cells, using flow cytometric sorting and quantitative real-time PCR (qPCR). Investigate dendritic cell-T cell interactions in HIV-2 infection including the ability of HIV-2 to be taken up, processed, and presented to HIV-2-specific CD4+ T cells. These studies will include an analysis of the ability of primary HIV-2 isolates to replicate in and/or activate plasmacytoid and myeloid dendritic cells (DC) and the ability of these DCs to transfer virus to antigen-specific CD4+ T cells.


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