Induction of terminal deoxynucleotidyl transferase and Lyt antigens with thymosin: identification of multiple subsets of prothymocytes in mouse bone marrow and spleen.

Abstract

Thymosin (fraction 5 and synthetic .alpha.1 peptide) induced prothymocytes in mouse bone marrow and spleen to express terminal deoxynucleotidyl transferase (TdT; DNA nucleotidylexotransferase; nucleosidetriphosphate:DNA deoxynucleotidylexotransferase, EC 2.7.7.31) or Lyt-1+,2+,3+ alloantigens (or both) after brief incubation in vitro. Three antigenic phenotypes were generated: TdT+Lyt+, TdT-Lyt+ and TdT+Lyt-. The TdT+Lyt+ phenotype was expressed by 80% of prothymocytes in bone marrow and 30% of prothymocytes in spleen from normal mice. The TdT-Lyt+ phenotype was expressed by 81% of prothymocytes in bone marrow from athymic mice. More than 80% of TdT+ bone marrow cells from normal and athymic mice expressed Lyt antigens after thymosin treatment. Most TdT+ hemopoietic cells in normal and athymic mice are thymocyte progenitors. Two independent lineages of prothymocytes exist, one that expresses TdT and another that does not. Commitment of prothymocytes to the TdT+ cell pathway is partially regulated by a thymic feedback mechanism. The bone marrow preferentially produces TdT+ prothymocytes; the spleen may serve as a repository for TdT- prothymocytes. A model of T cell development is presented in which the thymus functions as a compound organ to process TdT+ and TdT- thymocyte progenitors and to generate 2 lines of T cells.