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Age-Related CD8⁺ T Cell Clonal Expansions Express Elevated Levels of CD122 and CD127 and Display Defects in Perceiving Homeostatic Signals¹

Ilhem Messaoudi, Jessica Warner and Janko Nikolich-ugich²

Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006

Aging is accompanied by numerous changes in T cell biology. Among the most dramatic changes at the population level are the appearance and persistence of CD8⁺ T cell clonal expansions (TCE), whose frequency increases steadily with age, and whose biology is incompletely understood. In this study, we examined trafficking, phenotypic makeup, and homeostatic responsiveness of TCE, which arise spontaneously in specific pathogen-free mice. We show that these cells make up a specialized subset of central memory T cells with distinguishable phenotypic characteristics, most notably the higher expression of CD122 and CD127, molecules that make up IL-15R and IL-7R, respectively, than other memory T cells. We confirm that these cells proliferate at a continuous pace upon adoptive transfer into the eulymphoid recipient, unlike their non-TCE memory-phenotype counterparts, which remain undivided and die. However, upon transfer into lymphopenic recipients, TCE fail to rapidly expand, but rather resume their slow, continuous proliferation. The above results are discussed in light of possible mechanisms that afford selective survival advantage to TCE over other T cells in an aged T lymphocyte pool.

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 U.S. Public Health Service National Institutes of Health Awards AG20719 (to J.N.-.), 5T32 AI007472-10 (to I.M.), and RR0163 (to Oregon National Primate Research Center) from National Institute on Aging, National Institute of Allergy and Infectious Diseases, and National Institute for Research Resources, respectively.

² Address correspondence and reprint requests to Dr. Janko Nikolich-ugich, Vaccine and Gene Therapy Institute, Oregon Health & Science University West Campus, 505 Northwest 185th Avenue, Beaverton, OR 97006. E-mail address: nikolich{at}ohsu.edu

³ Abbreviations used in this paper: TCE, T cell clonal expansion; AI-TCE, Ag-independent TCE; AR-TCE, Ag-responding TCE; FCM, flow cytofluorometry; HPE, homeostatic proliferative expansion; int, intermediate; KO, knockout; SPF, specific pathogen free; T_CM, central memory T.

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