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Volume 6 Supplement 3

AIDS Vaccine 2009

P16-31. Skewed HIV-1-specific CD4+ Th2 helper cell contribution in progressive HIV-1 infection

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Background

CD4+ T helper cells play a crucial role in the orchestration of the immune system. While CD4+ Th1 responses provide important helper signals to the survival and maturation of CD8+ T cells, CD4+ Th2 responses are involved in B cell maturation and antibody class switching. However, very little is known about the role and contribution of HIV-1-specific CD4+ T helper responses to the control of viral replication. Here we show that the presence of Gag-specific CD4+ Th1 responses and Th2 responses against Env are associated with viral control, while changes in this pattern are associated with disease progression.

Methods

We cross-sectionally screened 21 subjects with chronic HIV-1 infection (>10,000 copies/mL) and 15 elite controllers (<50 copies/mL) for HIV-1-specific CD4+ T helper responses by flow cytometry before and after cultivation in helper subset polarizing conditions (Th1: IFNγ/IL12; Th2: IL4/anti-IFNγ; Th17: anti-IL4/anti-IFNγ/TGFβ/IL6).

Results

HIV-1-specific CD4+ T helper responses were detected in similar frequencies in chronic HIV-1 infection and elite controllers. However, we observed in HIV-1 elite controllers significantly more CD4+ T cell responses consisting of a Th1 (IFNγ+/IL2+) CD4+ T cell phenotype. These responses were predominantly directed against the HIV-1 Gag protein. In contrast, in subjects with chronic-progressive HIV-1 infection Th1 responses were directed against envelope in a higher frequency (p < 0.02). Interestingly, while the HIV-1-specific Th2 responses in elite controllers were preferentially directed against envelope, we observed a skewed over-representation of Th2 responses against Gag in subjects with chronic-progressive HIV-1 infection. These responses were also associated with higher activation levels.

Conclusion

Our data suggest that the presence of a distinct CD4+ T helper cell pattern is associated with viral control. The presence of Gag-specific Th1 responses and Env-specific Th2 responses suggests a potential important role for the helper signals for B and T cell responses. This finding might be highly important for vaccine design.

Author information

Correspondence to M Chevalier.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Chevalier, M., Pyo, A., Jolin, J. et al. P16-31. Skewed HIV-1-specific CD4+ Th2 helper cell contribution in progressive HIV-1 infection. Retrovirology 6, P260 (2009). https://doi.org/10.1186/1742-4690-6-S3-P260

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Keywords

  • Helper Cell
  • Viral Control
  • Elite Controller
  • Helper Response
  • Helper Subset