Substantial intrapatient differences in the breadth and specificity of HIV-specific CD8+ T-cell interferon-gamma and proliferation responses.

Abstract

HIV vaccine design and evaluation require a better understanding of protective immune responses. HIV-specific CD8+ T-cell responses have been characterized extensively using interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot (ELISPOT) assays, which do not always correlate with control of viral replication or disease progression. Alternative aspects of CD8+ T-cell responses, in particular those associated with a central memory (Tcm) phenotype, may be more protective against disease progression. To determine the extent that the breadth and specificity of HIV-specific CD8+ T-cell responses differ based on immunological readout, we screened in HIV-infected Kenyan sex workers for responses to HIV Env using IFN-gamma ELISPOT and 6-day carboxyfluorescein succinimidyl ester-based proliferation assays. This comparison revealed substantial differences in the epitopes recognized when the assay readout was IFN-gamma versus proliferation. Although 24 and 41 IFN-gamma and proliferative responses were identified, overlapping specificity was observed for only 5 responses. Breadth also differed between assays in several patients. Env-specific IFN-gamma breadth was found to correlate inversely with CD4 count (r = -0.66, P = 0.005), although this was not the case for proliferation. These data suggest that efforts to define HIV-specific CD8+ T-cell responses may need to be revisited using additional immunological readouts.

• Authors: Lyle R McKinnon, T Blake Ball, Charles Wachihi, Nyakio Chinga, Anne Maingi, Ma Luo, Keith R Fowke, Francis A Plummer
• Journal: Journal of acquired immune deficiency syndromes (1999) (J Acquir Immune Defic Syndr) Vol. 49 Issue 2 Pg. 123-7 (Oct 01 2008) ISSN: 1525-4135 [Print] United States
• PMID: 18769359 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes, T-Lymphocyte
• env Gene Products, Human Immunodeficiency Virus
• Interferon-gamma

Topics

• CD4 Lymphocyte Count
• CD8-Positive T-Lymphocytes (immunology)
• Cell Proliferation
• Epitopes, T-Lymphocyte (immunology)
• Female
• HIV Infections (immunology)
• Humans
• Interferon-gamma (biosynthesis)
• Kenya
• Sex Work
• env Gene Products, Human Immunodeficiency Virus (immunology)