Thymic stroma-derived T cell growth factor (TSTGF). IV. Capacity of TSTGF to promote the growth of L3T4- Lyt-2- thymocytes by synergy with phorbol myristate acetate or various IL.
The present study investigates the role of thymic stroma-derived T cell growth factor (TSTGF) in promoting the growth of L3T4- Lyt2- (double-negative) thymocytes. Partially purified TSTGF samples were prepared from the culture supernatant of a newly established thymic stromal cell line, MRL104.8a. The TSTGF alone induced only marginal proliferation of double-negative thymocytes, whereas this factor exerted a potent growth-promoting effect on these cells in combination with PMA. Because such an enhanced proliferation was not inhibited by anti-IL-4 or anti-IL-2R antibody, this was not due to the stimulation of an autocrine mechanism involving the production and utilization of IL-4 or IL-2. In scrutinizing PMA-equivalent physiologic substance(s), IL-1 was revealed to be capable of replacing the role of PMA in the above co-stimulation cultures and including enhanced proliferation of double-negative thymocytes in combination with TSTGF. Although TSTGF plus IL-2 or IL-4 also exhibited an appreciable or moderate synergistic effect on the growth of double-negative thymocytes, its magnitude was weaker compared with that obtained by TSTGF plus IL-1. More important, the strikingly enhanced proliferation was induced in the combinations of TSTGF, IL-1, and IL-2 or IL-4 under conditions in which the proliferation induced by IL-1 plus IL-4 or IL-1 plus IL-2 was marginal or slight. Furthermore, such strongly enhanced proliferation was also observed in the double-negative thymocyte population which was additionally depleted of T3+ cells (namely, the L3T4- Lyt-2- T3- or dull population). These results indicate the crucial role of TSTGF in the proliferation of immature thymocytes by synergy with various cytokines.
Mizushima
Y
Y
Biomedical Research Center, Osaka University Medical School, Japan.
Saitoh
M
M
Ogata
M
M
Kosaka
H
H
Tatsumi
Y
Y
Kiyotaki
C
C
Hamaoka
T
T
Fujiwara
H
H
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000502:physiology; D000375:Aging; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D002455:Cell Division / Q000187:drug effects; D004338:Drug Combinations; D004357:Drug Synergism; D005109:Extracellular Matrix / Q000502:physiology*; D007376:Interleukin-2 / Q000502:physiology*; D007378:Interleukins / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology* / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013950:Thymus Gland / Q000502:physiology*
D000276:Adjuvants, Immunologic; D000945:Antigens, Differentiation, T-Lymphocyte; D004338:Drug Combinations; D007376:Interleukin-2; D007378:Interleukins; D013755:Tetradecanoylphorbol Acetate