Paucity of IL-21-producing CD4+ T cells is associated with Th17 cell depletion in SIV infection of rhesus macaques

Luca Micci, Barbara Cervasi, Zachary S. Ende, Robin I. Iriele, Elane Reyes-Aviles, Carol Vinton, James Else, Guido Silvestri, Aftab A. Ansari, Francois Villinger, Savita G Pahwa, Jacob D. Estes, Jason M. Brenchley, Mirko Paiardini

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42 Scopus citations

Abstract

IL-21 regulates Th17 cell homeostasis, enhances the differentiation of memory B cells and antibody-secreting plasma cells, and promotes the maintenance of CD8+ T-cell responses. In this study, we investigated the phenotype, function, and frequency of blood and intestinal IL-21-producing cells in nonhuman primates that are hosts of progressive (rhesus macaques [RMs]) and nonprogressive (sooty mangabeys [SMs]) SIV infection. We found that, in both species, memory CD4+CD95+CCR6- T cells are the main IL-21 producers, and that only a small fraction of CD4+IL- 21+ T cells produce IL-17. During chronic SIV infection of RMs, CD4+IL-21+ T cells were significantly depleted in both blood and rectal mucosa, with the extent of this depletion correlating with the loss of Th17 cells. Furthermore, treatment with IL-21 increased the in vivo levels of Th17 cells in SIV-infected RMs. In contrast, normal levels of CD4 +IL- 21+ T cells were found in SIV-infected SMs. Collectively, these data indicate that depletion of IL-21-producing CD4 + T cells distinguishes progressive from nonprogressive SIV infection of RMs and SMs, and suggest that depletion of CD4+IL-21+ T cells is involved in the preferential loss of Th17 cells that is associated with SIV disease progression. Further preclinical studies of IL-21 as a potential immunotherapeutic agent for HIV infection may be warranted.

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ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Micci, L., Cervasi, B., Ende, Z. S., Iriele, R. I., Reyes-Aviles, E., Vinton, C., Else, J., Silvestri, G., Ansari, A. A., Villinger, F., Pahwa, S. G., Estes, J. D., Brenchley, J. M., & Paiardini, M. (2012). Paucity of IL-21-producing CD4+ T cells is associated with Th17 cell depletion in SIV infection of rhesus macaques. Blood, 120(19), 3925-3935. https://doi.org/10.1182/blood-2012-04-420240