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Preferential infection and depletion of Mycobacterium tuberculosis-specific CD4 T cells after HIV-1 infection.

Research paper by Christof C Geldmacher, Njabulo N Ngwenyama, Alexandra A Schuetz, Constantinos C Petrovas, Klaus K Reither, Edwin J EJ Heeregrave, Joseph P JP Casazza, David R DR Ambrozak, Mark M Louder, William W Ampofo, Georgios G Pollakis, Brenna B Hill, Erica E Sanga, Elmar E Saathoff, Leonard L Maboko, et al.

Indexed on: 01 Dec '10Published on: 01 Dec '10Published in: The Journal of experimental medicine



Abstract

HIV-1 infection results in the progressive loss of CD4 T cells. In this study, we address how different pathogen-specific CD4 T cells are affected by HIV infection and the cellular parameters involved. We found striking differences in the depletion rates between CD4 T cells to two common opportunistic pathogens, cytomegalovirus (CMV) and Mycobacterium tuberculosis (MTB). CMV-specific CD4 T cells persisted after HIV infection, whereas MTB-specific CD4 T cells were depleted rapidly. CMV-specific CD4 T cells expressed a mature phenotype and produced very little IL-2, but large amounts of MIP-1β. In contrast, MTB-specific CD4 T cells were less mature, and most produced IL-2 but not MIP-1β. Staphylococcal enterotoxin B-stimulated IL-2-producing cells were more susceptible to HIV infection in vitro than MIP-1β-producing cells. Moreover, IL-2 production was associated with expression of CD25, and neutralization of IL-2 completely abrogated productive HIV infection in vitro. HIV DNA was found to be most abundant in IL-2-producing cells, and least abundant in MIP-1β-producing MTB-specific CD4 T cells from HIV-infected subjects with active tuberculosis. These data support the hypothesis that differences in function affect the susceptibility of pathogen-specific CD4 T cells to HIV infection and depletion in vivo, providing a potential mechanism to explain the rapid loss of MTB-specific CD4 T cells after HIV infection.

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