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 of the spleen cell response previously reported, this cytotoxic activity requires in vivo priming. We performed several experiments designed to determine whether the in vivo priming effect is due to the in situ priming of the 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. We show by depletion of peripheral cells with antilymphocyte serum and part body irradiation 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 were also demonstrated to contribute to the thymus-derived CTL response. Thus, the minor H-specific thymic CTL response is due both to in situ priming and the immigration of activated peripheral T cells. We discuss the possible significance for models of T cell differentiation of the presence within the thymus of antigen and antigen-reactive mature T cells.

The Effect of Antigen Stimulation on the Migrationof Mature T Cells from the Peripheral Lymphoid Tissuesto the Thymus

“…There Was clearly an increase in the number of cells which migrated into the thymus following antigen-specific T cell activation in the periphery, confirming the findings of earlier studies (Naparstek et al, 1982;Fink et al, 1984;Agus et al, 1991;Bell et al, 1995;Westermann et al, 1996). This increase amounted to about 16 to 20-fold 3 days after injection with peptide.…”

“…Previous investigations of immigration of mature T cells to the thymus were limited by the fact that activated cells were defined and purified on the basis of cell-surface marker expression (Bell et al, 1995;Westermann et al, 1996), or involved adoptive transfer of previously activated cells (Fink et al, 1984;Agus et al, 1991). Additionally, measurement of immigrating cells has frequently relied upon relatively non-quantitative radioactive, immunohistochemical or in vitro cell culture techniques (Naparstek et al, 1982;Fink et al, 1984;Westermann et al, 1996).…”

Peripheral T Lymphocytes Recirculating Back into the Thymus Can Mediate Thymocyte Positive Selection

“…Early observations indicated that this phenomenon might be restricted to the neonatal period, a time when the periphery is lymphopenic, or to the recirculation of some activated T cells back to the adult thymus (5). Clearly, during an ongoing antiviral immune response, some degree of priming is seen among mature thymocytes (25,26). Using either parabiosis (6) or transfer of CFSE-labeled cells (27), we have previously shown that in a situation of peripheral lymphopenia, the contribution of recirculating peripheral T cells to the pool of mature "thymocytes" was significant.…”

Chemokines: signal lamps for trafficking of T and B cells for development and effector function

“…Other thymus-expressed chemokines, TARC, LARC, MDC/STCP-1, and murine TCA4, attract mature leukocytes: TARC attracts T cell lines [27]; LARC attracts resting lymphocytes [30]; MDC/STCP-1 attracts activated T cells, monocytederived dendritic cells, monocytes, and NK cells [24,25]; TCA4 attracts mature T cells and cultured mesangial cells [32]. Recirculation of mature T cells to thymus was suggested to be a negative regulation mechanism of T lymphopoiesis [37,38]. Thus, these thymus-expressed chemoattractants for mature T cells may have a role in T lymphopoiesis by regulating the trafficking of mature T cells into thymus.…”