Perturbed CD8 + T cell immunity across universal influenza epitopes in the elderly

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Thi H. O. Nguyen¹  Sneha Sant¹  Nicola L. Bird¹  Emma J. Grant¹  E. Bridie Clemens¹  Marios Koutsakos¹  Sophie A. Valkenburg¹  Stephanie Gras³  Martha Lappas⁶  Anthony Jaworowski⁸  Jane Crowe^1,10  Liyen Loh¹  Katherine Kedzierska¹ 

[1] Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity;Division of Infection and Immunity, Cardiff University School of Medicine, United Kingdom;Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University;Pasteur School of Public Health, The University of Hong Kong;Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University;Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, The University of Melbourne;Mercy Perinatal Research Centre, Mercy Hospital for Women;Department of Infectious Diseases, Alfred Hospital and Monash University;Centre for Biomedical Research, Burnet Institute;Deepdene Surgery

关键词: TCR repertoire;    transcription factors;    ZAP-70;    CD8+ T cells;    aging;   

DOI  :  10.1189/jlb.5MA0517-207R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Influenza epidemics lead to severe illness, life-threatening complications, and deaths, especially in the elderly. As CD8+ T cells are associated with rapid recovery from influenza, we investigated the effects of aging on antigen-specific CD8+ T cells across the universal influenza epitopes in humans. We show that aging is characterized by altered frequencies in T cell subsets, with naive T cells being partially replaced by activated effector/memory populations. Although we observed no striking differences in TCR signaling capacity, T cells in the elderly had increased expression of transcription factors Eomes and T-bet, and such changes were most apparent in CD8+ T cells. Strikingly, the numbers of antigen-specific CD8+ T cells across universal influenza epitopes were reduced in the elderly, although their effector/memory phenotypes remained stable. To understand whether diminished numbers of influenza-specific CD8+ T cells in the elderly resulted from alteration in TCR clonotypes, we dissected the TCR?? repertoire specific for the prominent HLA-A*02:01-restricted-M158–66 (A2/M158) influenza epitope. We provide the first ex vivo data on paired antigen-specific TCR?? clonotypes in the elderly, showing that influenzaspecific A2/M158+ TCR?? repertoires in the elderly adults varied from those in younger adults, with the main features being a reduction in the frequency of the public TRAV27–TRBV19 TCR?? clonotype, increased proportion of private TCR?? signatures, broader use of TRAV and TRBV gene segments, and large clonal expansion of private TCR?? clonotypes with longer CDR3 loops. Our.

【 授权许可】

CC BY