Diversity and clonal selection in the human T-cell repertoire

Proceedings of the National Academy of Sciences of the United States of America - Tập 111 Số 36 - Trang 13139-13144 - 2014
Qian Qi1, Yi Liu2,3, Yong Cheng4, Jacob Glanville5,6, David Zhang7, Ji-Yeun Lee2, Richard A. Olshen8,9, Cornelia M. Weyand10,11, Scott D. Boyd2, Jörg J. Goronzy10,7
1Divisions of Immunology and Rheumatology, Department of Medicine and.
2Departments of cPathology,
3Stanford Center for Biomedical Informatics Research, and Departments of Pathology.
4Genetics, and
5Departments of Pathology, Immunology, Stanford University, Stanford, CA 94305; and.
6Immunology, Stanford University, Stanford, CA 94305; and
7Divisions of aImmunology and Rheumatology, Department of Medicine and
8Biostatistics
9fBiostatistics,
10Department of Medicine, VA Palo Alto Health Care System, Palo Alto, CA 94306
11Divisions of Immunology and Rheumatology, Department of Medicine and Department of Medicine, VA Palo Alto Health Care System, Palo Alto, CA 94306

Tóm tắt

SignificanceA decline in the diversity of the T-cell receptor repertoire owing to thymic involution has been implicated as causing defective immune responses in the elderly. By applying next-generation sequencing of replicate TCRB libraries from highly purified T-cell subsets, and using nonparametric statistical analysis, we obtain estimates of repertoire richness in the young adult that are higher than previously reported. Although contracting with age, the repertoire remains highly diverse. These data challenge the paradigm that thymic rejuvenation is needed to maintain diversity and prevent immune incompetence in the elderly. However, we observe an increasing inequality of clonal sizes with age even among naïve T cells. This clonal selection could result in biased and possibly autoreactive immune responses.

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Thông tin xuất bản

Proceedings of the National Academy of Sciences of the United States of America

Tập 111 Số 36

13139-13144

Thông tin tác giả