Extrathymic human t lymphocyte development and regulation in immune deficient mice

Abstract

Abstract We previously studied extrathymic human T lymphocyte development from stem/progenitor subsets in the bone marrow of bnx mice. Current studies examined human T cell development from purified CD34 + CD3 − stem cells in a new strain that we developed, nude/NOD/SCID mice. Human T cells isolated from bnx mice contained double CD4 + /CD8 + and single CD3 + /CD4 + or CD3 + /CD8 + cells, but they were anergic to activation by PMA plus ionomycin (P+1) and to CD3 and CD28 crosslinking. In nude/NOD/SCID mice, there was more variability in human T cell development in the marrow. Double positive CD4/CD8 and CD4 + /cytoCD3 + populations, which expressed CD3 mRNA, were found in some of the mice. But no CD8 single positive cells were found in any mice. In some mice, only myeloid progenitor cells and B cells were found, much like the NOD/SCID strain. The differences may be due to different microenvironments or to the types of human cells engrafted in the starting populations. Studying the influence of implanting human pediatric thymus slices into nude/NOD/SCID on the development of human T cells is in progress. Thymus grafts get well vascularized in the peritoneal cavity of mice. Early studies suggest that the presence of the thymus makes the human T cells less hyporesponsive. Future studies will detemine whether the human cells are being selected in the thymus or whether thymic stromal factors are influencing development and/or activation of human T cells.