(1) Gustafson CE (2) Qi Q (3) Hutter-Saunders J (4) Gupta S (5) Jadhav R (6) Newell E (7) Maecker H (8) Weyand CM (9) Goronzy JJ
(1) Gustafson CE (2) Qi Q (3) Hutter-Saunders J (4) Gupta S (5) Jadhav R (6) Newell E (7) Maecker H (8) Weyand CM (9) Goronzy JJ
Aging is associated with an increased susceptibility to infection and a failure to control latent viruses thought to be driven, at least in part, by alterations in CD8 T cell function. The aging T cell repertoire is characterized by an accumulation of effector CD8 T cells, many of which express the negative regulatory receptor CD85j. To define the biological significance of CD85j expression on CD8 T cells and to address the question whether presence of CD85j in older individuals is beneficial or detrimental for immune function, we examined the specific attributes of CD8 T cells expressing CD85j as well as the functional role of CD85j in antigen-specific CD8 T cell responses during immune aging. Here, we show that CD85j is mainly expressed by terminally differentiated effector (TEMRAs) CD8 T cells, which increase with age, in cytomegalovirus (CMV) infection and in males. CD85j+ CMV-specific cells demonstrate clonal expansion. However, TCR diversity is similar between CD85j+ and CD85j- compartments, suggesting that CD85j does not directly impact the repertoire of antigen-specific cells. Further phenotypic and functional analyses revealed that CD85j identifies a specific subset of CMV-responsive CD8 T cells that coexpress a marker of senescence (CD57) but retain polyfunctional cytokine production and expression of cytotoxic mediators. Blocking CD85j binding enhanced proliferation of CMV-specific CD8 T cells upon antigen stimulation but did not alter polyfunctional cytokine production. Taken together, these data demonstrate that CD85j characterizes a population of "senescent," but not exhausted antigen-specific effector CD8 T cells and indicates that CD85j is an important checkpoint regulator controlling expansion of virus-specific T cells during aging. Inhibition of CD85j activity may be a mechanism to promote stronger CD8 T cell effector responses during immune aging.
Author Info: (1) Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA, United States. Department of Medicine, Palo Alto Veterans Administration Hea
Author Info: (1) Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA, United States. Department of Medicine, Palo Alto Veterans Administration Healthcare System, Palo Alto, CA, United States. (2) Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA, United States. Department of Medicine, Palo Alto Veterans Administration Healthcare System, Palo Alto, CA, United States. (3) Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA, United States. Department of Medicine, Palo Alto Veterans Administration Healthcare System, Palo Alto, CA, United States. (4) Department of Microbiology and Immunology, Stanford University, Stanford, CA, United States. (5) Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA, United States. Department of Medicine, Palo Alto Veterans Administration Healthcare System, Palo Alto, CA, United States. (6) Department of Microbiology and Immunology, Stanford University, Stanford, CA, United States. Agency for Science, Technology and Research (ASTAR), Singapore Immunology Network (SIgN), Singapore, Singapore. (7) Department of Microbiology and Immunology, Stanford University, Stanford, CA, United States. (8) Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA, United States. Department of Medicine, Palo Alto Veterans Administration Healthcare System, Palo Alto, CA, United States. (9) Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA, United States. Department of Medicine, Palo Alto Veterans Administration Healthcare System, Palo Alto, CA, United States.
Citation: Front Immunol 2017 8:692 Epub06/14/2017
