Abnormal activation and loss of suppressor T cells in the spontaneously hypertensive rat.
Suppressor T cell function in the spontaneously hypertensive rat (SHR) and normotensive Wistar Kyoto (WKY) rats was analyzed using syngeneic mixed lymphocyte reaction (SMLR) and concanavalin A (Con A) activation. A depressed SMLR was found in adult SHR but not in adult WKY. IL-2 synthesized by SHR was 40-fold lower than that of WKY, and the suppressor T cells generated in the SMLR were incapable of suppressing IgG synthesis. Precursors of cells that can be activated by Con A to become functional suppressor cells are reduced in adult SHR. Supernatant fluids derived from Con A-activated spleen cells from adult SHR failed to significantly inhibit IgG synthesis by cultures of syngeneic spleen cells compared to supernatant fluids from young SHR or WKY Con A-activated spleen cells. However, spleen cells from both adult SHR and WKY proliferated strongly and released equivalent amounts of IL-2 in response to Con A. Addition of exogenous IL-2 to the SMLR cultures in vitro restored the ability of SHR T cells to respond in the SMLR, with generation of cells capable of suppressing IgG synthesis. Administration of SHR with IL-2 in vivo also restored the suppressor T cell function in the SMLR. These results suggest a defective suppressor T cell activation and loss of suppressor T cell activity as the SHR age.
Ofosu-Appiah
W
W
Masonic Medical Research Laboratory, Utica, New York 13501.
Ruggiero
C
C
D000818:Animals; D002478:Cells, Cultured; D003208:Concanavalin A; D006973:Hypertension / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007213:Indomethacin / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013154:Spleen / Q000276:immunology; D013491:Suppressor Factors, Immunologic / Q000096:biosynthesis; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
D007074:Immunoglobulin G; D007376:Interleukin-2; D013491:Suppressor Factors, Immunologic; D003208:Concanavalin A; D007213:Indomethacin