Ontogenesis of Cell-Mediated Immunity in Murine Thymocytes and Spleen Cells and its Acceleration by Thymosin, a Thymic Hormone

Abstract

Abstract The ontogenesis of the cell-mediated immunologic capacity of spleen cells and thymocytes of CBA/Wh mice was studied from day 19 of embryonic life through 60 days of age. Two indices of immunologic competence were used, namely, the capacity of donor CBA/Wh cells to elicit a graft-vs-host (GVH) response in adult, lethally irradiated B6AF1/J mice and the mixed lymphocyte interaction (MLI) in vitro. In addition, the influence of a thymic humoral factor (thymosin) on the rate of maturation of cells from spleens of neonatal CBA/Wh mice and from bone marrow of adult CBA/Wh mice was investigated. The results of this study indicate that the capacity of thymocytes to elicit a GVH response and their ability to participate in a MLI developed within the first hours after parturition. Spleen cells, however, did not acquire the capacity to elicit positive responses in either one of these assays until 3 or 4 days postnatally. Administration of thymosin in vivo to newborn CBA/Wh mice or in vitro incubation of lymphoid stem cell populations with thymosin significantly accelerated the development of the capacity of spleen cells to elicit a GVH response. The ability of thymocytes to elicit a GVH response, once developed with a given number of cells, remained constant throughout the study period of 60 days. In contrast, the marked response of newborn CBA/Wh thymocytes to (CBA/Wh × C57BL/6)F1 spleen cells in the MLI decreased rapidly with age, suggesting a loss of recognition capacity or an alteration in cell types within the thymic population. The data support the concept of an endocrine role for the thymus in the development and maturation of lymphoid cells that participate in cell-mediated immune responses.