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IL-2 production correlates with effector cell differentiation in HIV-specific CD8+ T cells.

  • Author(s): Nomura, Laurel E;
  • Emu, Brinda;
  • Hoh, Rebecca;
  • Haaland, Perry;
  • Deeks, Steven G;
  • Martin, Jeffrey N;
  • McCune, Joseph M;
  • Nixon, Douglas F;
  • Maecker, Holden T
  • et al.
Abstract

Background

Diminished IL-2 production and lack of effector differentiation have been reported for HIV-specific T cells. In this study, we examined the prevalence of these phenomena using 8-color cytokine flow cytometry, and tested the hypothesis that these two findings were causally related. We analyzed cytokine profiles and memory/effector phenotypes of HIV-specific and CMV-specific T cells using short-term in vitro stimulation with HIV or CMV peptide pools. Nineteen HIV-positive subjects with progressive disease and twenty healthy, HIV-negative subjects were examined.

Results

Among HIV-infected subjects, there were significantly fewer CD8+ IL-2+ T cells responding to HIV compared to CMV, with no significant difference in CD4+ IL-2+ T cells. The majority of CMV-specific T cells in both HIV-negative and HIV-positive subjects appeared to be terminally differentiated effector cells (CD8+ CD27- CD28- CD45RA+ or CD8+ CD27- CD28- CD45RA-). In HIV-positive subjects, the most common phenotype of HIV-specific T cells was intermediate in differentiation (CD8+ CD27+ CD28- CD45RA-). These differences were statistically significant, both as absolute cell frequencies and as percentages. There was a significant correlation between the absolute number of HIV-specific CD8+ IL-2+ T cells and HIV-specific CD8+ CD27- CD28- CD45RA+ terminal effector cells.

Conclusion

IL-2 production from antigen-specific CD8+ T cells correlates with effector cell differentiation of those cells.

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