Tumor antigen drives a persistent oligoclonal expansion of CD8+ T cells in aged mice.
Oligoclonal T cell expansions (TCE) are common in old humans and mice, but it is not known whether the T cell response to a specific antigen is more restricted in old vs. young animals. Herein, we describe an enhanced and prolonged response of tumor antigen-specific CD8 cells in old mice identified by K(d)/peptide tetramers and Vbeta10 staining. At the onset of the response CD8 T cell numbers and Vbeta10+CD8+ cells at the site of tumor injection were lower in old mice, hinting that control of initial tumor growth may not be optimal. As further evidence of a dysregulated response in old mice, antibody titers to the tumor were deficient and the CD8 tumor antigen-specific response was greater and more prolonged in the blood and spleen. Old mice selected a more oligoclonal TCR repertoire based on TCRbeta chain CDR3 length analysis and sequences. Persistent expansions of Vbeta10+CD8+ cells in old mice had memory/activation phenotypes. This induced tumor antigen-specific response may represent a model for the spontaneous TCE observed with aging and demonstrates that the CD8 response to a defined peptide/MHC antigen is indeed more oligoclonal in old mice.
Li
Fang
F
Immunology Program, Graduate School of Medical Sciences, Weil Medical College of Cornell University, New York, NY 10021, USA.
Yarilin
Dmitri A
DA
Valiando
Jennifer
J
Ronco
Amy
A
Weksler
Marc E
ME
Szabo
Paul
P
Posnett
David N
DN
D000375:Aging / Q000276:immunology*; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D022801:Complementarity Determining Regions; D016130:Immunophenotyping; D051379:Mice; D008811:Mice, Inbred DBA; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry
D000951:Antigens, Neoplasm; D022801:Complementarity Determining Regions; D011948:Receptors, Antigen, T-Cell