Abstract

In the present study the effect of aging on the capacity of Ia+ cells to stimulate autoreactive T cells in the syngeneic mixed lymphocyte reaction (SMLR) was investigated. Using young CD4+ T cells as responders, it was observed that unseparated whole spleen cells from aged mice had normal stimulatory activity comparable to that of young spleen cells. Interestingly, however, when purified splenic adherant cells (SAC) enriched for macrophages or splenic B cells were used as stimulators, aged SAC but not aged B cells were found to be defective in stimulating autoreactive T cells. This defect in aged SAC was not due to decreased expression of Ia antigens since the percentage of Ia+ SAC and density of Ia antigen expression was similar in both young and old mice. Also, the B cells from aged mice expressed normal levels of Ia antigens. Aged SAC, when mixed with young SAC could also actively suppress the normal SMLR. However, this suppression was not due to increased prostaglandin production but was found to be associated with interleukin-1 (IL-1) regulation, inasmuch as addition of exogenous IL-1 could completely reconstitute the defective stimulatory activity of aged SAC and also abolished the suppressor activity of the SAC. Aged mice also demonstrated an intrinsic defect in the CD4+ T cells responding in the SMLR. Together, our studies on the SMLR demonstrate an age-related defect in responder autoreactive T cells and in stimulator splenic macrophages but not in the stimulatory activity of B cells.

Document Type

Article

Publication Date

1990

Notes/Citation Information

© 1990 Elsevier Scientific Publishers Ireland Ltd.

Digital Object Identifier (DOI)

https://doi.org/10.1016/0047-6374(90)90118-Y

Funding Information

Supported in part by the NIH grants CA45009 and CA45010 to P.N. and M.N., and AI 21490, AG-05731 to B.S. who is also the recipient of a Research Career Development award, AG 00422. Address all correspondence to: Dr. Prakash S. Nagarkatti, Dept. of Biology, Derring Hall, Virginia Polytechnic Institute and State University Blacksburg, VA 24061, U.S.A.

Download

Share

COinS