Role of the spleen in ontogenic development of phytomitogen response in thymus of CBA mice.
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Biomedical subjects
Publications and source records attributed to M Papiernik.
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Cultures of pure epithelial cells have been obtained from human thymus. Incubation of spleen cells from adult thymectomized mice on these cultures rendered RFC sensitive to inhibition by anti-theta serum, whereas no effect was obtained with fibroblasts or spleen cell cultures. The fact that theta conversion was obtained when spleen cells were incubated in the thymic culture placed within a Millipore chamber indicates that theta conversion was due to the effect of a humoral factor.
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IL-6 has been demonstrated by in vitro studies to be a cytokine involved in thymocyte activation We show herein that thymocytes cultured at high concentrations in the absence of comitogen respond to IL-1 and, to a lesser degree, to GM-CSF, by producing IL-6. This phenomenon disappears rapidly with decreasing cell densities, suggesting the involvement of a minor cellular component of the thymus which may be solely responsible for or cooperate in IL-6 production. We have analysed several thymic subpopulations for IL-6 production and show that accessory cells, and eventually their precursors, are the major if not exclusive, producers of this cytokine. Mature steroid-resistant thymocytes do not secrete IL-6. Production of IL-6 by total CD4-CD8- thymic cells is largely reduced by the depletion of mature accessory cells which express I-A and Mac-1 antigens. As shown previously, accessory cell precursors within the CD4-CD8- compartment are induced to differentiate into M phi and DC in response to IL-1 and GM-CSF. We provide evidence that this maturation is associated with IL-6 production. Thymic DC and phagocytic cells of the thymic reticulum (P-TR) in vitro produce high levels of IL-6 which are enhanced by GM-CSF or IL-1. These factors have a synergistic effect on IL-6 production by total thymocytes, and on CD4-CD8- cells that are not depleted for mature I-A+ Mac-1+ accessory cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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We investigated the physiological role of IL-4 in the thymus and spleen by administering a neutralizing monoclonal anti-IL-4 antibody (11B11 mAb) into adult mice for 7 or 14 days. After this treatment the thymus decreased in size, this was mainly attributed to a decrease in the CD4+CD8+ subset after 7 days and both the CD4+CD8+ and the CD4+CD8- subsets after 14 days. These data suggest that IL-4 has a role in CD4+CD8+ thymocyte development and can differentially modulate the maturation of CD4+CD8- thymocytes in adult mice. Conversely, anti-IL-4 inoculation induced an increase in spleen size. After 7 days of treatment this enlargement appeared to be due to a increase in number of immature cells, the majority of which were CD4-CD8-alpha beta TCR-B220-slg-Ia-Mac-1-Pgp1 positive. After 14 days, an expanded spleen size was mainly due to inflated numbers of mature CD4+CD8-, B and Mac-1+ cells. In addition, we showed that anti-IL4 mAb in vivo enhanced the CD4-CD8-alpha beta TCRlow subset within the spleen after 7 days which is also observed at 14 days of treatment. Finally, we demonstrated that anti-IL-4 mAb treatment is highly stimulatory for hemopoietic activity in the adult spleen. Taken together, these results support the notion that IL-4 acts in vivo, directly or indirectly, on T cell differentiation in the thymus and T subsets homeostasis as well as on other cell types in the spleen of adult mice.