Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 38, Issue 2, Pages 350-363Publisher
WILEY
DOI: 10.1002/eji.200737768
Keywords
chemokines; cytokines; HIV; T cells
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Funding
- Medical Research Council [MC_U137884180, MC_U190081958] Funding Source: researchfish
- MRC [MC_U137884180, MC_U190081958] Funding Source: UKRI
- Intramural NIH HHS [Z99 AI999999] Funding Source: Medline
- Medical Research Council [MC_U137884180, MC_U190081958] Funding Source: Medline
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HIV-2 is distinguished clinically and immunologically from HIV-1 infection by delayed disease progression and maintenance of HIV-specific CD4(+) T cell help in most infected subjects. Thus, HIV-2 provides a unique natural human model in which to investigate correlates of immune protection against HIV disease progression. Here, we report a detailed assessment of the HIV-2-specific CD4(+) and CD8(+) T cell response compared to HIV-1, using polychromatic flow cytometry to assess the quality of the HIV-specific T cell response by measuring IFN-gamma, IL-2, TNF-alpha, MIP-1 beta, and CD107a mobilization (degranulation) simultaneously following Gag peptide stimulation. We find that HIV-2-specific CD4(+) and CD8(+) T cells are more polyfunctional that those specific for HIV-1 and that polyfunctional HIV-2-specific Tcells produce more IFN-gamma and TNF-alpha on a per-cell basis than monofunctional T cells. Polyfunctional HIV-2-specific CD4(+) T cells were generally more differentiated and expressed CD57, while there was no association between function and phenotype in the CD8(+) T cell fraction. Polyfunctional HIV-specific T cell responses are a hallmark of non-progressive HIV-2 infection and may be related to good clinical outcome in this setting.
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