Journal
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
Volume 56, Issue 3, Pages 213-221Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAI.0b013e3181ff2aba
Keywords
acute HIV infection; primary HIV infection; CD8(+) T cells; T cell proliferation; interleukin-2; polyfunctional
Categories
Funding
- National Institutes of Health [R01 AI084772, R21 AI73103, R01 AI064060, AIDERP UO1 A101008, MO-RR00032, P30 AI27767]
- University of Alabama at Birmingham
- National Institutes of Health, National Center for Research Resources [5UL1 RR025777-03]
- American Society of Physiology [5T36GM73062]
- University of Alabama at Birmingham, Center for AIDS Research Flow cytometry core [P30AIO27767]
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Understanding the correlates of immunity that control HIV-1 infection is imperative to our understanding of HIV-1 disease and vaccine development. HIV-1-specific cytotoxic T lymphocytes are fundamental to the control of viremia; however, which T-cell repertoire components enact this control remains unclear. We hypothesize that polyfunctional HIV-1-specific CD8 T cells capable of viral control are present in most patients early in infection and these cells are distinguished by their ability to secrete interleukin (IL)-2 and proliferate. We examined HIV-1-specific CD8 T-cell proliferation and cytokine secretion in primary HIV-1 infection (PHI) using known HIV-1 cytotoxic T-cell epitopes to exclude CD4 bystander effect. We found that only a subset of patients with PHI demonstrated CD4-independent'' CD8 proliferation ex vivo. The remainder of the patients lacked HIV-1-specific CD8 T cells with proliferative capacity, even after the addition of exogenous IL-2. Among the proliferators, IL-2 production from the total HIV-specific CD8 T-cell population correlated with proliferation. Surprisingly, though, we did not routinely detect both IL-2 secretion and proliferative capacity from the same antigen-specific CD8 T cells. Thus, there are distinct and heterogeneous populations of CD8 T cells, phenotypically characterized by either proliferation or IL-2 secretion and few with dual capacity. Generation of these responses may be an important measure of HIV-1 control but are not universal after PHI. Furthermore, the heterogeneity of this population suggests that a simple measure of an effective vaccine response remains elusive.
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