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Volume 9 Supplement 2

AIDS Vaccine 2012

  • Poster presentation
  • Open Access

Recombinant IL-21 induces perforin and granzyme B in total and virus specific CD8 Tcells in acute and early stages of SIV infection in rhesus macaques

  • 1,
  • 2,
  • 2,
  • 2,
  • 2,
  • 2,
  • 2 and
  • 3
Retrovirology20129 (Suppl 2) :P13

https://doi.org/10.1186/1742-4690-9-S2-P13

  • Published:

Keywords

  • Post Infection
  • Rhesus Macaque
  • Cytotoxic Potential
  • Rectal Biopsy
  • Vaccine Strategy

Background

We have recently demonstrated that the cytokine IL-21 enhances the cytotoxic potential of CD8 T cells in chronically SIV infected rhesus macaques (vaccines 2011).

Methods

In this study, 12 RM were infected with SIVmac239 (i.v., 300 TCID50). rMamu IL 21-Fc fusion protein (50mg/kg) was given s.c on a weekly basis post infection (pi) for 5 doses on days14, 21, 28, 35 and 42pi to 6 animals, designated as “treated”, with 3 mamuA01+ animals each in treated and control groups. Samples of PBMC, bone marrow (BM), rectal biopsy (RB) and peripheral LN (LN) were collected before infection (d-11), and at various times post infection.

Results

Compared to controls, IL-21 treated animals demonstrated increases in frequency and MFI of Perforin (Perf) and granzyme B (GrB) at d45 in total CD8 T cells in PBMC, LN and RB, particularly in CM and Effector subsets; these were sustained up to d70pi. Perf and GrB levels increased in virus specific Tet+ CD8 T cells at d 45 in PBMC (p=0.029), LN (p=0.015), and RB (p=0.024). In the CD4 T cells, GrB induction was more prominent in the PBMC, LN, BM and RB. Frequencies of CD4 (p=0.011) and CD8 (p=0.031) CM T cells increased in PBMC at d70pi. T cell inhibitory molecule PD-1 and proliferation marker Ki67 were similar in treated and control animals. In treated animals, 2/6 showed a decline in post-peak viremia that was sustained up to d70pi follow up.

Conclusion

In summary, IL-21 given s/c to SIV infected RM during early stages of infection led to augmented T cell cytotoxic granules perf and GrB in total and virus specific CD8 T cells in various anatomical sites. IL-21 should be explored further in vaccine strategies as an immunomodulating adjuvant.

Authors’ Affiliations

(1)
University of Miami, Miami, FL, USA
(2)
Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA
(3)
University of Miami Miller School of Medicine, Miami, FL, USA

Copyright

© Pallikkuth et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://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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