Impaired autoreactive T cell-induced T cell-T cell interaction in aged mice.
Self-Ia-reactive (autoreactive) L3T4+ T cell clones have been shown earlier to stimulate the proliferation of syngeneic naive L3T4+ T cells and initiate a T cell-T cell (T-T) interaction leading to the generation of immunoregulatory circuits. Since aging has been shown to be associated with a decline of the immune responsiveness, age-related alterations in the T-T interaction was investigated in the present study. Using several I-Ed-specific autoreactive T cell clones isolated from 2- to 3-month-old (young) DBA/2 mice as stimulators, it was observed that L3T4+ T cells from 22- to 24-month-old (aged) DBA/2 mice, failed to demonstrate a significant response to the autoreactive T cells. In contrast, L3T4+ T cells from young mice responded strongly to the autoreactive T cell clones. The deficient T-T cell interaction in aged mice correlated with an impaired syngeneic mixed lymphocyte reaction in these mice, thereby suggesting that aging induces a defect both in the autoreactive T cells and in T cells which react with the autoreactive T cells. When exogenous recombinant interleukin 2 (rIL-2), recombinant interleukin 4 (rIL-4), or a combination of these was added to the interaction, it was observed that rIL-4 but not rIL-2 enhanced the T-T interaction in young mice. However, rIL-4 or a combination of rIL-2 and rIL-4 failed to correct the defective T-T interaction in aged mice. Since the T cell network is believed to play an important role in the maintenance of normal immune system homeostasis, the present study suggests that age-related alterations in T and B cell functions and increased susceptibility to autoimmune diseases with age may result from a defect in the T cell network regulation.
Udhayakumar
V
V
Department of Microbiology and Immunology, University of Kentucky, Lexington 40536.
Subbarao
B
B
Seth
A
A
Nagarkatti
M
M
Nagarkatti
P S
PS
D000375:Aging / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D002455:Cell Division; D002460:Cell Line; D003470:Culture Media; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D003470:Culture Media; D007376:Interleukin-2; D007378:Interleukins; D011994:Recombinant Proteins; D015847:Interleukin-4