Clonal anergy blocks the response to IL-4, as well as the production of IL-2, in dual-producing T helper cell clones.
In this report we extend the in vitro clonal anergy model to examine the regulation of proliferation in T cells that secrete both IL-2 and IL-4. Newly cloned Ag-specific murine T cells are shown to depend on both IL-2 and IL-4 synthesis for maximal proliferation. Whereas IL-2 responsiveness is constitutive in these cells, IL-4 responsiveness develops only after Ag and APC stimulation. Remarkably, proliferation of these cells to Ag is sensitive to inhibition by clonal anergy, even though IL-4 synthesis remains inducible. Anergy in these cells is associated with an inability to respond to IL-4, in addition to the development of an IL-2 production defect. The results suggest that anergy induction may be capable of preventing the clonal expansion of autoreactive T cells producing both IL-2 and IL-4 in vivo.
Mueller
D L
DL
Harold C. Simmons Arthritis Research Center, Dallas, TX.
Chiodetti
L
L
Bacon
P A
PA
Schwartz
R H
RH
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D000941:Antigens / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells; D007376:Interleukin-2 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
D000941:Antigens; D007376:Interleukin-2; D015847:Interleukin-4