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

TitleDistinctive features of CD4+ T cell dysfunction in chronic viral infections.
Publication TypeJournal Article
Year of Publication2014
AuthorsMorou A, Palmer BE, Kaufmann DE
JournalCurr Opin HIV AIDS
Volume9
Issue5
Pagination446-51
Date Published09/01/2014
ISSN1746-6318
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.

DOI10.1097/COH.0000000000000094
Alternate JournalCurr Opin HIV AIDS
PubMed ID25023623
Grant ListP01 AI-080192 / AI / NIAID NIH HHS / United States
R01 HL-092565 / HL / NHLBI NIH HHS / United States
UM1AI100663 / AI / NIAID NIH HHS / United States
UO1 HL098996 / HL / NHLBI NIH HHS / United States
UO1 HL13026 / HL / NHLBI NIH HHS / United States
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