Skip to main content

Volume 6 Supplement 3

AIDS Vaccine 2009

P16-47. Interleukin (IL)-21 induces cytolytic molecule perforin in CD4 and CD8 T cells without CD4 activation in chronically SIV infected rhesus macaques

Background

IL-21 is a common g-chain utilizing cytokine derived mainly from activated CD4 T cells and T follicular helper cells with a broad range of cellular targets. We previously described perforin induction by IL-21 in human CD8 T cells with dependence on prior cellular activation and Stat-3 utilization (Blood, 2007).

Methods

To confirm its biologic activity, we conducted pilot in vivo studies of r-Mamu IL-21 in rhesus macaques.

Results

In two healthy animals a dose escalation study (1, 10, 50 and 100 microgram/kg subcutaneous IL-21 at 14 day intervals) resulted in a modest transient increase in perforin in T cells. There were no adverse events but anti-IL-21 antibody mainly to his-tag was rapidly induced. In 4 chronically SIV infected animals, IL-21 injections (2 doses, 50 microgram/kg intravenously at 7 day intervals; 3rd dose 100 microgramg/kg subcutaneously 21 days after the 2nd dose) resulted in significant upregulation of perforin at all doses in CD4 and CD8 T cells in peripheral blood sampled on day 3 post dosing in comparison to 3 SIV+ control animals. Interestingly, perforin increase was noted in all CD4 and CD8 T cell subsets (naive, central memory, effector memory) and fold increase was most prominent in naïve CD4 cells (2.7 fold, P = 0.05) and effector memory CD8 T cells (2 fold, P = 0.0004). Perforin upregulation was accompanied by slight increase in Ki67 in CD8 T cells, but with no evidence of cellular expansion and significant decrease in HLA-DR expression in naïve and central memory CD4 T cells. No change in CD4 counts or virus load were noted. Functional virus specific T cell responses and serum anti-IL-21 determination are ongoing.

Conclusion

The novel perforin inducing property of IL-21 in CD4 and CD8 T cells without inducing CD4 T cell activation makes it an attractive molecule for consideration in immunotherapeutic and vaccine strategies.

Author information

Affiliations

Authors

Corresponding author

Correspondence to S Pahwa.

Rights and permissions

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.

Reprints and Permissions

About this article

Cite this article

Pahwa, S., Pallikkuth, S., Rogers, K. et al. P16-47. Interleukin (IL)-21 induces cytolytic molecule perforin in CD4 and CD8 T cells without CD4 activation in chronically SIV infected rhesus macaques. Retrovirology 6, P276 (2009). https://doi.org/10.1186/1742-4690-6-S3-P276

Download citation

Keywords

  • Rhesus Macaque
  • Central Memory
  • Follicular Helper
  • Infected Rhesus
  • Follicular Helper Cell