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Current Opinion in HIV & AIDS:
doi: 10.1097/COH.0000000000000094
CELL EXHAUSTION IN HIV-1 INFECTION: Edited by Daniel E. Kaufmann and Nabila Seddiki

Distinctive features of CD4+ T cell dysfunction in chronic viral infections

Morou, Antigonia; Palmer, Brent E.b; Kaufmann, Daniel E.a,c

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Abstract

Purpose of review: To describe recent advances in the understanding of virus-specific CD4+ T cell dysfunction in chronic viral infections, with an emphasis on HIV disease. We highlight features that are distinctive for CD4+ T cells, as opposed to their CD8+ T cell counterparts.

Recent findings: CD4+ T cell activation and differentiation are tightly controlled. Regulation of these processes depends on the context of initial encounter of the naïve CD4+ T cell with the cognate antigen and on ongoing external cues to the antigen-experienced CD4+ T cell, in particular the inflammatory environment, which is prominent in HIV infection. Virus-specific CD4+ T cell dysfunction results from a combination of an exhaustion program and skewing in T helper lineage differentiation which impact function. The CD4+ and CD8+ T cell exhaustion programs present similarities and distinct features. The sets of inhibitory coreceptors expression differ, although programmed-death 1 (PD-1) and T cell immunoglobulin mucin-3 (Tim-3) are upregulated on both HIV-specific CD4+ and CD8+ T cells, cytotoxic T-lymphocyte antigen 4 (CTLA-4) is largely specific to CD4+ T cells, whereas 2B4 and CD160 are biased toward CD8+ T cells.

Summary: Understanding the molecular basis of HIV-specific CD4+ T cell exhaustion and identifying key differences with CD8+ T cell impairment will be critical to design effective therapeutic and preventive immunotherapies against HIV.

© 2014 Lippincott Williams & Wilkins, Inc.

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