Impaired Autoreactive T Cell-Induced T Cell-T Cell Interaction in Aged Mice

Authors

Venkatachalam Udhayakumar, University of Kentucky
Subbarao Bondada, University of KentuckyFollow
Aruna Seth, Virginia Polytechnic Institute and State University
Mitzi Nagarkatti, Virginia Polytechnic Institute and State University
Prakash S. Nagarkatti, Virginia Polytechnic Institute and State University

Abstract

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-E^d-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.

Document Type

Article

Publication Date

1988

Notes/Citation Information

Copyright © 1988 by Academic Press, Inc.

Digital Object Identifier (DOI)

https://doi.org/10.1016/0008-8749(88)90232-8

Funding Information

The work at Virginia Polytechnic Institute and State University was supported by National Institute of Health Grants CA 45009 and CA 45010 and a BRSG grant awarded to P.S.N. and M.N. and the work at University of Kentucky was supported by National Institute of Health Grants AI 2 1490 and AG 0573 1, awarded to B.S.

Repository Citation

Udhayakumar, Venkatachalam; Bondada, Subbarao; Seth, Aruna; Nagarkatti, Mitzi; and Nagarkatti, Prakash S., "Impaired Autoreactive T Cell-Induced T Cell-T Cell Interaction in Aged Mice" (1988). Microbiology, Immunology, and Molecular Genetics Faculty Publications. 192.
https://uknowledge.uky.edu/microbio_facpub/192