HIV-specific CD8+ T-cell proliferation is prospectively associated with delayed disease progression.

Abstract

Human immunodeficiency virus (HIV)-specific CD8(+) T-cell proliferation is consistently correlated with enhanced host HIV immune control, but whether proliferative responses are a cause or consequence of immune protection is unclear. We measured Env-specific CD8(+) T-cell proliferation and interferon (IFN)-γ secretion in HIV-infected participants with CD4 counts >200, who then completed 121 person-years of prospective follow-up to monitor HIV disease progression. In all, 13 of 31 participants (42%) reached end point during longitudinal follow-up. Strong Env-specific CD8(+) T-cell proliferation (>10% of CD8(+) T cells) was observed in 14/31 participants at baseline, and this was associated with a longer time to HIV disease progression end point, stratified baseline CD4 count (P=0.016). No associations were observed for IFN-γ ELISPOT responses and progression (P>0.2). Strong proliferation remained significant in multivariate Cox regression analyses (P=0.044) as an independent predictor of delayed HIV disease progression, along with baseline CD4 count (P=0.04). Duration of HIV infection was associated with more rapid progression in univariate, but not multivariate, analysis (P=0.112). Age and baseline viral load were not predictive of progression. HIV-specific CD8(+) T-cell proliferation was a correlate of protective immunity in this prospective study; such responses may be important for HIV vaccine protection.

• Authors: Lyle R McKinnon, Rupert Kaul, Joshua Kimani, Nico J Nagelkerke, Charles Wachihi, Keith R Fowke, Terry Blake Ball, Francis A Plummer
• Journal: Immunology and cell biology (Immunol Cell Biol) Vol. 90 Issue 3 Pg. 346-51 (Mar 2012) ISSN: 1440-1711 [Electronic] United States
• PMID: 21606945 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• env Gene Products, Human Immunodeficiency Virus
• Interferon-gamma

Topics

• Adult
• CD4 Lymphocyte Count
• CD8-Positive T-Lymphocytes (immunology, metabolism, pathology)
• Cell Proliferation
• Cells, Cultured
• Disease Progression
• Disease-Free Survival
• Enzyme-Linked Immunospot Assay
• Female
• Follow-Up Studies
• HIV (immunology)
• HIV Infections (diagnosis, immunology, physiopathology)
• Humans
• Interferon-gamma (metabolism)
• Lymphocyte Activation
• Male
• Prospective Studies
• env Gene Products, Human Immunodeficiency Virus (immunology, metabolism)