REPOPULATION KINETICS OF INTESTINAL INTRAEPITHELIAL LYMPHOCYTES IN MURINE BONE-MARROW RADIATION CHIMERAS

The kinetics of lymphoid cell repopulation of murine intestinal intraepithelial lymphocytes (IEL) from BM stem cells were studied in F1 --> parent radiation chimeras and were compared with T cell repopulation of the thymus and the spleen. T cells arising from donor bone marrow were present in the gut epithelium as early as day 5 postreconstitution in radiation chimeras. By day 7 postreconstitution, and at times thereafter, the IEL consisted of 70-95% CD3+ donor bone marrow-derived T cells, most of which were CD8+ cells with variable Thy-1 expression. CD4+8- IEL also were detected between days 7 and 14 postreconstitution; however, the CD4+8+ IEL subset did not appear within the gut epithelium until several weeks later and was followed by a progressive increase in the intensity of CD8 expression on CD4+8+ IEL. Functionally mature T cell receptor gamma/delta+ and alpha/beta+ IEL were present throughout repopulation of the gut epithelium. In contrast to the IEL, T cells were not detected in the thymus or the spleen until days 14 and 21 postreconstitution, respectively, and evidence of T cell function in the spleen was not detected until day 21 postreconstitution. These findings have implications for human bone marrow transplantation in that they demonstrate that T cell repopulation of the gut epithelium begins prior to T cell repopulation of the thymus and the spleen, and indicate that even in the presence of a thymus some IEL proceed through an extrathymic developmental pathway.