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Volume 6 Supplement 3

AIDS Vaccine 2009

P16-32. Antigen exposure regulates the balance between proliferating and cytotoxic subsets of virus-specific CD8 T-cells

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Background

Cytotoxicity and proliferation are key functions of CD8 T-cells whose relationship remains unclear. We recently showed that perforin, more than GrmB, and unlike GrmA and K, is correlated with cytotoxicity. CD127 (IL-7Ra) has been suggested as a marker of proliferation capacity. Here we investigated the relationship between cytotoxicity and proliferation in different viral infections.

Methods

Virus-specific CD8 T-cell responses (n = 74) including CMV, EBV, Flu and HIV-1 were characterized using tetramer complexes or peptide stimulation and analyzed for proliferation capacity, expression of CD127 and perforin. CCR7, CD45RA, PD-1 and CD57 were used to assess T-cell differentiation/exhaustion. Simultaneous expression of IFNγ, IL-2, TNFα and perforin was analysed by polychromatic flow cytometry.

Results

We first confirmed the association between CD127 expression and proliferation capacity (P < 0.01) in virus-specific CD8 T-cell responses. Combined expression of perforin and CD127 revealed the existence of three populations of CD8 T-cells: CD127+perforin-, CD127-perforin- and CD127-perforin+ which were mostly CD45RA-CCR7+, CD45RA-CCR7- and CD45RA+CCR7- CD8 T-cells, respectively. CD127-perforin+ was CD57+, whereas CD127-perforin- had higher PD-1 expression (P < 0.002). Furthermore, CD127+perforin- represented the large majority (90%) of Flu-specific CD8 T-cells; CD127-perforin- were the majority (64%) of EBV-specific CD8 T-cells; and CD127-perforin+ were dominant for CMV-specific CD8 T-cells (43%). HIV-specific CD8 T-cells were mostly CD127-perforin-. These differences were significant (all P < 0.002). Of note, we observed a negative correlation between perforin and CD127 expression in virus-specific CD8 T-cells (P < 0.001). Consistently, ICS on CMV-specific CD8 T-cells confirmed the lack of co-expression of perforin and IL-2, which is known to correlate with proliferation. Finally, changes in antigen exposure in vitro, or in vivo during primary HIV-1 infection, modulated CD127 expression, as previously showed for perforin.

Conclusion

Proliferative (CD127+/IL-2-secreting) and cytotoxic (perforin+) CD8 T-cells are distinct T-cell subsets that are at different stages of differentiation. The balance between proliferation and cytotoxic capacity appears to be influenced by antigen exposure.

Author information

Correspondence to C Cellerai.

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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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Cellerai, C., Perreau, M., Rozot, V. et al. P16-32. Antigen exposure regulates the balance between proliferating and cytotoxic subsets of virus-specific CD8 T-cells. Retrovirology 6, P261 (2009). https://doi.org/10.1186/1742-4690-6-S3-P261

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Keywords

  • CD127 Expression
  • Proliferation Capacity
  • Antigen Exposure
  • Peptide Stimulation
  • Tetramer Complex