Thymic cytotoxic T lymphocytes are primed in vivo to minor histocompatibility antigens.

Abstract

Potent cytotoxic T lymphocyte (CTL) activity can be derived from cultures of thymocyte responders and minor H different spleen cell stimulators. As is the case for the spleen cell response previously reported, this cytotoxic activity requires in vivo priming. Several experiments were designed to determine whether the in vivo priming effect is due to the in situ priming of [mouse] thymocyte CTL precursors, to contamination of thymus cell preparations with cells of neighboring lymph nodes, or to the appearance in the thymus of antigen-reactive peripheral T cells. By depletion of peripheral cells with antilymphocyte serum and part body irradiation it was shown that recent thymic immigrants derived from the bone marrow contribute to the primed thymic response. Thymic CTL were primed in animals in which peripheral T cell responses were completely eliminated by repeated treatment in vivo with monoclonal anti-Thy-1 reagents. Primed, antigen-activated lymph node cells also contributed to the thymus-derived CTL response. The minor H-specific thymic CTL response is due both to in situ priming and the immigration of activated peripheral T cells. The possible significance for models of T cell differentiation of the presence within the thymus of antigen and antigen-reactive mature T cells is discussed.