Development of cytotoxic T lymphocyte precursors in the absence of the thymus.

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AbstractReconstitution of adult thymectomized and lethally irradiated C3H or (C 3 H × DBA/2) F1 mice with syngeneic adult bone marrow cells or 18 to 20‐day‐old fetal liver cells resulted almost regularly in the generation of large numbers of cytotoxic T lymphocyte precursors (CTLP) against trinitrophenylated C3H cells and three types of allogeneic stimulator and target cells. The responses against 2,4,6‐ trinitrophenylated cells were restricted and in so far typical for cytotoxic T lymphocytes.The failure of bone marrow cells from athymic C 3 H mice to reconstitute significant cytotoxic activity indicated that the CTLP had developed from “cytotoxic T lymphocyte preprogenitors” (CTLPP) which were derived from the donor and which had already been under thymic influence. The stem cell preparations in themselves contained frequencies of mature CTLP far too low to account for the reactivity and CTLP frequencies in the reconstituted mice. This fact implied that the CTLPP proliferated extensively and/or matured in the recipient in the absence of the thymus.Individual mice failed to respond to one or more of these stimulator cells. The failure of individual mice to respond was randomly expressed for the four specificities even when the mice were reconstituted with the same stem cell preparation suggesting that CTLPP with defined specificity and low frequency (about 1/108 in fetal liver) were contained in the stem cell preparation and transferred randomly into the irradiated recipients. This would imply that one CTLPP gives rise to 5 × 103–20 × 103 CTLP within 5 weeks.The data suggest that the peripheral pools, at least of certain T cell subclasses, may be maintained largely by post‐thymic proliferation of CTLPP.