HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ahmed, M. Articles by Blackman, M. A. Search for Related Content PubMed PubMed Citation Articles by Ahmed, M. Articles by Blackman, M. A.

Clonal Expansions and Loss of Receptor Diversity in the Naive CD8 T Cell Repertoire of Aged Mice¹

Trudeau Institute, Saranac Lake, NY 12983

There are well-characterized age-related changes in the peripheral repertoire of CD8 T cells characterized by reductions in the ratio of naive:memory T cells and the development of large clonal expansions in the memory pool. In addition, the TCR repertoire of naive T cells is reduced with aging. Because a diverse repertoire of naive T cells is essential for a vigorous response to new infections and vaccinations, there is much interest in understanding the mechanisms responsible for declining repertoire diversity. It has been proposed that one reason for declining repertoire diversity in the naive T cell pool is an increasing dependence on homeostatic proliferation in the absence of new thymic emigrants for maintenance of the naive peripheral pool. In this study, we have analyzed the naive CD8 T cell repertoire in young and aged mice by DNA spectratype and sequence analysis. Our data show that naive T cells from aged mice have perturbed spectratype profiles compared with the normally Gaussian spectratype profiles characteristic of naive CD8 T cells from young mice. In addition, DNA sequence analysis formally demonstrated a loss of diversity associated with skewed spectratype profiles. Unexpectedly, we found multiple repeats of the same sequence in naive T cells from aged but not young mice, consistent with clonal expansions previously described only in the memory T cell pool. Clonal expansions among naive T cells suggests dysregulation in the normal homeostatic proliferative mechanisms that operate in young mice to maintain diversity in the naive T cell repertoire.

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 National Institutes of Health grants (AG022175 and AG021600) and the Trudeau Institute (to M.A.B.).

² Current address: Division of Rheumatology, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Rangos Research Center, Pittsburgh PA 15213.

³ Address correspondence and reprint requests to Dr. Marcia A. Blackman, Trudeau Institute, 154 Algonquin Avenue, Saranac Lake, NY 12983. E-mail address: mblackman{at}trudeauinstitute.org

This article has been cited by other articles:

				L. Boding, C. M. Bonefeld, B. L. Nielsen, J. P. H. Lauritsen, M. R. von Essen, A. K. Hansen, J. M. Larsen, M. M. Nielsen, N. Odum, and C. Geisler TCR Down-Regulation Controls T Cell Homeostasis J. Immunol., October 15, 2009; 183(8): 4994 - 5005. [Abstract] [Full Text] [PDF]