Modulation of T-cell differentiation in murine fetal thymus organ cultures.
The effects of IL-1, IL-2, and a panel of monoclonal antibodies to thymic stroma and/or thymocytes, on T-cell differentiation in murine fetal thymus organ cultures were followed. Day-14 fetal thymic lobes were cultured for up to 12 days in the presence of IL-1 and/or IL-2 at concentrations of 100 U/ml. Development of all the major subpopulations defined by CD4 and CD8 expression was inhibited by IL-2, however the degree of inhibition was greatest for CD4+CD8- and CD4+CD8+ subsets. IL-1 alone caused only minor shifts in the subpopulations, but when added together with IL-2 the inhibitory effects of IL-2 were markedly enhanced. Analyses of subsets of CD4-CD8- cells demonstrated that the inhibition was most dramatic at the IL-2R positive and subsequent stages of CD4-CD8- differentiation. Interestingly, the putative precursors of IL-2R+CD4-CD8- increased in the presence of IL-2. In preliminary studies the organ culture system was used to examine the effects of a panel of antibodies to thymocytes and/or thymic stromal cells. Out of 14 antibodies tested, MTS 35 and MTS 37 have caused relative increases in the CD8 and CD4 single-positives, respectively. Both antibodies also induced increases in the percentages of CD4-CD8- cells and decreases in the percentages of CD4+CD8+ cells.
Waanders
G A
GA
Department of Pathology and Immunology, Monash Medical School, Prahran, Melbourne, Australia.
Godfrey
D I
DI
Boyd
R L
RL
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D002454:Cell Differentiation; D005333:Fetus / Q000166:cytology; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D051379:Mice; D008808:Mice, Inbred CBA; D009924:Organ Culture Techniques; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology*
D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D007375:Interleukin-1; D007376:Interleukin-2