Developmental control of lymphokine gene expression in fetal thymocytes during T-cell ontogeny.

Abstract

We have used the technique of in situ hybridization to investigate the expression of lymphokine genes by immature thymocytes during intrathymic development. In 13-day fetal thymocytes a population of cells constitutively produces low levels of interleukin 2 (IL-2) and interleukin 4 (IL-4) mRNAs. A second phase of lymphokine gene expression occurs in the majority of 15-day thymocytes, and a population of cells constitutively produces both IL-2 and IL-4 mRNAs. Thymocytes at 14 days of gestation and after 16 days up until birth do not express detectable lymphokine mRNA. By contrast, the population of IL-2 receptor mRNA-producing thymocytes increases progressively up to 15 days of gestation, and expression thereafter decreases up to birth. In addition, thymocytes expressing interferon y mRNA were not present until just prior to birth. Our fmdings indicate developmental control of lymphokine and lymphokine receptor gene expression in fetal thymocytes during ontogeny.A central issue of T-cell ontogeny is the identification of the signals and growth factors required for the proliferation and differentiation of immature cells in the thymus. Studies seeking to examine this issue by measuring the production and use of growth factors by thymocytes have depended on the stimulation of these cells by phorbol esters and ionophores outside the thymic environment (1-5). These results may not be representative ofevents inside the intact organ for several reasons. First, the activating agents are not physiological, and second, cells stimulated in this way do not undergo normal maturation or full T-cell receptor gene rearrangement. In addition, the development of thymocytes within the thymus may in part be dependent upon the coordinated production of growth factors by different populations of cells throughout ontogeny. Thus, the use of such potent stimulating agents as phorbol esters and ionophores to induce lymphokine production by immature thymocytes in vitro may mask or abrogate the regulated production of these growth factors by thymocytes that would occur in vivo.

Diminished Contact Hypersensitivity Response in IL‐4 Deficient Mice at a Late Phase of the Elicitation Reaction

“…Previously, IL-4 has been reported to promote growth and differentiation of T cell precursors in the fetal thymus at 14 to 15 days gestation [22]. It was possible to detect IL-4 mRNA in day 13 and day 15 fetal thymocytes [29]. Thus IL-4 is produced before the fetal thymic precursors of DETC have left the thymus to migrate to the epidermis [30,31].…”

Heterogeneity of thymic epithelial cells in promoting T-lymphocyte differentiation in vivo.

“…The synthesis of RNA for IL-7 and/or IL-la by EA2, ET, and EB3 epithelial cells is of potential significance because these cytokines were found to contribute to growth in vitro of thymocytes (24)(25)(26). The other two known growth factors for thymocytes, IL-2 and IL-4, are produced by the developing thymocytes themselves (27,28). The presence of IL-7 RNA transcripts in the thymus has been reported (29), but the cell types producing IL-7 mRNA were not identified.…”

Developmental Expression of IL‐2‐Receptor Light Chain (CD25) in the Chicken Embryo

“…These so-called TcR0 cells capacity of isolated intra-TNC lymphocytes to probably represent avian natural killer-cell equiva-mediate graft-versus-host reactions in the chorionallents (Bucy et al, 1990) and expand when the lantoic membrane assay (Penninger et al, 1989, chicken embryo undergoes graft-versus-host reac-1990 CD4, and CD8), thus allowing formation of highaffinity heterodimeric IL-2R and autocrine proliferation via the IL-2/IL-2R pathway (Toribio et al, 1989). The inducibility of both IL-2 and CD25 is developmentally controlled, that is, is restricted to certain thymocyte populations (Boyer et al, 1989;Carding et al, 1989). Under in vitro culture conditions, IL-2 is capable of inducing CD3, TcR, CD4, and CD8 surface expression on immature thymocytes (Toribio et al, 1988 Martinez-A., 1990).…”