Assessment of alloreactive T cell subpopulations of aged mice in vivo. CD4+ but not CD8+ T cell-mediated rejection response declines with advanced age.
The present investigation explored age-related alterations in T cell populations mediating allospecific responses in vivo. Healthy aged and young H-2b and H-2bxH-2k mice were engrafted with major histocompatibility complex (MHC) class II-disparate bm12 skin, rejection of which requires CD8+ T cells, and MHC class I-disparate bm1 skin, rejection of which requires CD8+ T cells. Aged mice of both genders exhibited prolonged survival of bm12 skin grafts relative to their young counterparts but rejected bm1 skin grafts at a rate equivalent to that of young mice. Consistent with prolonged survival of bm12 skin grafts, markedly diminished levels of Iabm12 CTL activity were elicited from T cells of aged mice in vitro. However, no such decline was observed in the level of Kbm1 CTL from T cells of aged mice. The alterations in Iabm12 allospecific responses were not attributable to quantitative changes in CD4+ T cells of aged mice, and addition of soluble T cell helper factors to response cultures of aged mice did not augment Iabm12 cytotoxic T lymphocytes activity. These data demonstrate that aging fundamentally affects CD4+ T cell-mediated allospecific responses particularly in vivo, and that deficient generation of soluble T cell helper factors alone cannot explain this deficit.
Rosenberg
A S
AS
Division of Hematologic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892.
Sechler
J M
JM
Horvath
J A
JA
Maniero
T G
TG
Bloom
E T
ET
D000375:Aging / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000502:physiology; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D007376:Interleukin-2 / Q000502:physiology; D007519:Isoantigens / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D016038:Skin Transplantation / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016827:CD8 Antigens; D007376:Interleukin-2; D007519:Isoantigens