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IL-21 Induces Apoptosis of Antigen-Specific CD8⁺ T Lymphocytes¹

Brianne R. Barker^*, Jenny G. Parvani^*, Debra Meyer, Adam S. Hey, Kresten Skak and Norman L. Letvin^2,*

^* Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115; Department of Biochemistry, University of Johannesburg, Auckland Park, South Africa; Antibody Pharmacology, Symphogen, Lyngby, Denmark; and Cancer Pharmacology, Novo Nordisk, Maalov, Denmark

IL-21, a member of the common -chain family of cytokines, has pleiotropic effects on T, B, and NK cells. We found that IL-21 and the prototype common -chain cytokine IL-2 can stimulate proliferation and cytokine secretion by Ag-specific rhesus monkey CD8⁺ T cells. However, unique among the members of this family of cytokines, we found that IL-21 drives these cells to apoptosis by down-regulation of Bcl-2. These findings suggest that IL-21 may play an important role in the contraction of CD8⁺ T cell responses.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Harvard University Center for AIDS Research, a National Institutes of Health-funded program (P30 AI060354).

² Address correspondence and reprint requests to Dr. Norman L. Letvin, Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, RE 113, P.O. Box 15732, Boston, MA 02215. E-mail address: nletvin{at}bidmc.harvard.edu

³ Abbreviation used in this paper: pSTAT, phosphorylated STAT.

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