Defect of thymocyte emigration in a T cell deficiency strain (CTS) of the mouse.

As bone marrow progenitors migrate to the thymus, differentiate into immunologically competent T cells, then leave the thymus and home to the peripheral lymphoid organs, each migration or homing is an essentially critical process for T cell differentiation. Homing of thymocytes into peripheral lymphoid organs has been extensively analyzed. On the contrary, little is known about the mechanism whereby mature thymocytes emigrate from the thymus to peripheral lymphoid organs. In this work, we show that the mutant T cell deficiency strain (CTS) of mouse, previously described as a peripheral T cell deficiency strain, has a novel defect of mature thymocyte emigration process. Flow-cytometric analysis demonstrated a marked decrease in T lymphocytes in peripheral lymphoid organs and an accumulation of mature thymocytes in the thymus. Histologic study revealed the high concentration of thymocytes within the giant perivascular space at thymic corticomedullary junction. These accumulating cells closely resemble normal peripheral T lymphocytes in terms of cell surface phenotype and responsiveness to mitogens or allogeneic cells. They were found to express the Mel-14 Ag, the homing receptor to lymph nodes, and had a high capability of homing to peripheral lymphoid organs when explanted thymocytes were injected i.v. The intrathymic labeling methods detected hardly any emigrating CTS thymocytes from the thymus. These results indicate that emigration defect lies in the thymus of CTS mice, and suggest that this mutation is due to abnormal releasing mechanisms occurring between the thymus and the bloodstream. Complete delineation of the precise mechanisms of this defect, however, requires further studies.