Endogenously secreted IL-4 is required for mouse thymocytes to become cytotoxic. Human, but not mouse, IL-2 induces a functionally immature thymic subset to secrete IL-4 and become CTL.
Experiments described here demonstrate that the differentiation of mouse thymocytes into cytotoxic T lymphocytes (CTL) requires interleukin-4 (IL-4). To reach this conclusion, we took advantage of our discovery that human and mouse IL-2 have very different effects on the development of CTL from a functionally immature subset of thymocytes. The lobster agglutinin 1 (LAg1)-negative subpopulation of thymocytes proliferated when cultured with concanavalin A (Con A)+ human or mouse IL-2, but these cells became CTL only when cultured with Con A+ human IL-2. Furthermore, Con A+ human IL-2, but not mouse IL-2, stimulated IL-4 production by cells within this population. Con A-induced cytotoxicity by mature LAg1-positive thymocytes and normal thymocytes was also accompanied by secretion of IL-4. The anti-IL-4 mAb 11B11 inhibited induction of cytotoxicity by all thymocyte populations tested. Taken together these experiments indicate that stimuli which induce cytotoxicity by mouse thymocytes also induce the secretion of IL-4, which is necessary for the differentiation of thymocyte CTL precursors into CTL.
Department of Medicine, National Jewish Center for Immunology & Respiratory Medicine, Denver, CO 80206.
K E
KE
Stedman
L B
LB
Justement
P A
PA
Campbell
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology*; D037102:Lectins / Q000032:analysis; D051379:Mice; D008815:Mice, Inbred Strains; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D007376:Interleukin-2; D037102:Lectins; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D015847:Interleukin-4