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 Fl → 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 γ/δ⁺ and α/β⁺ 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.