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Generation and Growth of CD28^nullCD8⁺ Memory T Cells Mediated by IL-15 and Its Induced Cytokines¹

^* Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224

Accumulation of CD28^nullCD8⁺ T cells and the defects of these cells in response to antigenic stimulation are the hallmarks of age-associated decline of T cell function. However, the mechanism of these age-associated changes is not fully understood. In this study, we report an analysis of the growth of human CD28^null and CD28⁺CD8⁺ memory T cells in response to homeostatic cytokine IL-15 in vitro. We showed that 1) there was no proliferative defect of CD28^nullCD8⁺ memory T cells in response to IL-15 compared with their CD28⁺ counterparts; 2) stable loss of CD28 expression occurred in those actively dividing CD28⁺CD8⁺ memory T cells responding to IL-15; 3) the loss of CD28 was in part mediated by TNF- that was induced by IL-15; and 4) CCL4 (MIP-1), also induced by IL-15, had a significant inhibitory effect on the growth of CD28^null cells, which in turn down-regulated their expression of CCL4 receptor CCR5. Together, these findings demonstrate that CD28^nullCD8⁺ memory T cells proliferate normally in response to IL-15 and that IL-15 and its induced cytokines regulate the generation and growth of CD28^nullCD8⁺ T cells, suggesting a possible role of IL-15 in the increase in CD28^nullCD8⁺ T cells that occurs with aging.

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 Intramural Research Program of the National Institute on Aging, National Institutes of Health.

² Address correspondence and reprint requests to Dr. Nan-ping Weng, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Box 21, Baltimore, MD 21224. E-mail address: wengn{at}mail.nih.gov

³ Abbreviations used in this paper: _c, common -chain; PI, proliferation index.

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