Newly generated CD4 T cells in aged animals do not exhibit age-related defects in response to antigen.
Using a T cell receptor transgenic (TCR Tg) mouse model, we have shown that TCR Tg CD4 cells from aged mice retain a naive phenotype, but exhibit reduced proliferation and IL-2 production in response to the antigen compared with cells from young mice. We hypothesize that age-related decreases in T cell function may be partly related to the age of the T cells. Because thymic output is decreased with age, peripheral T cells in older individuals are likely to be older than those in younger individuals. To investigate this possibility, we have manipulated the age of CD4 T cells in the periphery of young and aged mice. The production of new T cells was induced by depleting peripheral CD4 T cells or by creating bone marrow chimeras. In both young and aged individuals where we induced the production of new T cells, these newly generated cells exhibited robust responses to antigen ex vivo and in vivo, exhibiting good expansion, IL-2 production, and cognate helper function. Our results suggest that age-related defects in response to antigenic stimulation, in part, are caused by the age of the CD4 T cells.
Haynes
Laura
L
Trudeau Institute, Saranac Lake, NY 12983, USA. lhaynes@trudeauinstitute.org
Eaton
Sheri M
SM
Burns
Eve M
EM
Randall
Troy D
TD
Swain
Susan L
SL
D000375:Aging / Q000276:immunology* / Q000473:pathology; D000818:Animals; D000941:Antigens / Q000276:immunology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000473:pathology; D018183:Transplantation Chimera / Q000276:immunology
D000941:Antigens; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell