Inhibition of interleukin-2 synthesis and interleukin-2 receptor alpha expression on T cells by a cell-free factor derived from a CD4+ regulatory T cell clone.
We have shown that certain CD4+ T cell lines can function as suppressor cells in a cell culture system. In this context, the CD4+ T cells (AS-9) cloned from the peripheral blood lymphocytes (PBL) of a melanoma patient are capable of suppressing the induction of cytolytic response in autologous PBL in coculture. Here we show that a trypsin-sensitive cell-free culture supernatant factor from the AS-9 cells, AS-9 SF, interferes with IL-2 synthesis by T cells when they are stimulated. AS-9 SF also selectively blocks the expression of interleukin-2 receptor alpha (IL-2R alpha) on T cells during activation. Expression of transferrin receptors and the CD3 molecules is not down-regulated by this factor. The AS-9 SF consequently blocks proliferation of T cells when they are stimulated by lectin or activated through the T cell receptors. AS-9 SF suppresses the IL-2R alpha induction and the T cell proliferation at the induction phase only because it has no suppressive effect on preactivated T cells. Interleukin-2, IL-2R alpha, and beta messages are not down-regulated by the AS-9 SF and the suppressive effect of the AS-9 SF on IL-2R alpha expression and on T cell proliferation is not neutralized by the addition of exogenous recombinant IL-2. The factor does not appear to be IL-4, IL-10, or TGF-beta, three known cytokines possessing regulatory properties on T cell activation.
Okino
T
T
Department of Medicine, University of Connecticut Health Center, Farmington 06030.
Chakraborty
N G
NG
Stabach
P
P
Twardzik
D R
DR
Padula
S J
SJ
Mukherji
B
B
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D015870:Gene Expression; D006801:Humans; D007166:Immunosuppressive Agents; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000502:physiology; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4 / Q000502:physiology; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000502:physiology
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4