IL 7-induced T cell receptor-gamma gene expression by pre-T cells in murine fetal liver cultures.
IL-7 has previously been shown to stimulate proliferation of immature CD4-CD8- thymocytes from fetal and adult mice. We show that IL-7 mRNA levels are much higher in the day-14 fetal thymus than in the adult thymus, i.e., when the thymus is primarily composed of CD4-CD8- cells. Inasmuch as IL-7 may, therefore, be one of the first cytokines to which pre-T cells from the fetal liver are exposed when they migrate to the thymus during development, we hypothesized that IL-7 may promote differentiation of pre-T cells from the fetal liver. We found that human rIL-7 promotes growth of cells obtained from the liver of fetal mice at day 14 of gestation. Moreover, we found that IL-7 stimulated expression of mRNA encoding TCR-gamma, alpha-, and beta-genes. The size of the transcripts induced by IL-7 suggests that TCR-gamma was expressed in a rearranged form in response to IL-7, whereas TCR-alpha and -beta genes appeared to be expressed from nonrearranged loci. Culture of fetal liver cells for 7 days with IL-7 also caused the appearance of a population of cells expressing Thy-1 and Pgp-1 Ag, a phenotype similar to that seen in the early (day-14) fetal thymus. The Thy-1+ Pgp-1+ population was enriched in TCR-gamma mRNA, as determined by flow cytometric sorting followed by Northern blot analysis. These data support the hypothesis that IL-7 can stimulate some of the early events associated with thymocyte differentiation in the fetus.
Appasamy
P M
PM
Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, PA 15213.
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D002478:Cells, Cultured; D005260:Female; D005333:Fetus / Q000276:immunology*; D015870:Gene Expression / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D015851:Interleukin-7 / Q000235:genetics / Q000494:pharmacology*; D008099:Liver / Q000276:immunology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics; D020395:Receptors, Interleukin-7; D013601:T-Lymphocytes / Q000276:immunology*
D000954:Antigens, Surface; D015851:Interleukin-7; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic; D020395:Receptors, Interleukin-7