We have previously described extrathymic generation of human T cells from purified stem cells in the bone marrow of athymic immune deficient mice. This system provides a pure population of extrathymic human T cells that is devoid of contamination by peripheral expansion of thymic-selected T cells. In the current studies, we phenotypically compared the extrathymic human T cells (Ex-T) to T cells from human peripheral blood leukocytes (PBL), umbilical cord blood (CB), bone marrow (BM), and postnatal thymus. There were few CD4(+)/CD8(+) double positive (DP) cells in PBL, CB, BM, and Ex-T, in comparison with over 85% DP cells in thymus. More CD8(+) and CD4(dim) cells were observed in Ex-T than in the thymic-selected cells. Ex-T and T cells in thymus and peripheral tissues differed in their CD8 isoforms. There were more TCRgamma/delta T cells in PBL, CB, BM, and Ex-T than in thymus. Similar to the bright CD3(+) T cells in thymus, T cells in PBL, CB, and BM were CD3 bright and expressed the adhesion molecules CD44 and L-selectin (CD62L), while intermediate CD3 T cells in thymus lacked CD44 and L-selectin. However, the majority of Ex-T only expressed CD44 but not L-selectin. In summary, thymic- and extrathymic-derived T cells are phenotypically different. The identification of extrathymically derived T cells in humans will allow us to begin to understand their role in the early contribution to immune recovery posttransplantation and their possible involvement in autoimmunity and other disease states.
Copyright 2001 Academic Press.