Cytokine effects on the down regulation of cytolytic T cell responses in vitro.
Lymphocytes from mouse and men can be stimulated by a variety of cellular signals including concanavalin A and the interferons to generate cells capable of non-specific down regulation of the generation of immune responses. The studies reported here extend this finding to show that such regulatory cells are also generated during the course of a mixed lymphocyte response and following stimulation of the CD3 component of the T cell receptor with anti-CD3 antibody. Regulatory activity was assessed by the addition of putative regulatory cells to mixed lymphocyte cultures and measuring the generation of cytolytic T cell activity in these cultures. The action of such non-specific regulatory cells was blocked by antiserum to the N-terminal sequence of soluble immune response suppressor (SIRS). In addition, generation of the regulatory cell population was inhibited by antiserum to the 55 kd subunit of the IL-2 receptor. A survey of cytokines showed that while IL-2 was able to stimulate the generation of non-specific regulatory cell activity, IL-1,3,6,7, and 10 as well as TNF alpha and TGF beta were unable to generate such activity. IL-2 was unable to generate non-specific suppressive activity in the presence of anti-IL-2 receptor antibody. The regulatory activity of cells generated by IL-2 was inhibited by the anti-SIRS antiserum.
Terajima
C
C
Institute of Biological Sciences and Immunology, Syntex (USA) Inc, Palo Alto, CA.
Koontz
A
A
Kelley
M
M
Webb
D R
DR
Devens
B H
BH
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013491:Suppressor Factors, Immunologic / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects*
D016207:Cytokines; D015375:Receptors, Interleukin-2; D013491:Suppressor Factors, Immunologic; C013256:soluble immune response suppressor