A continuous but low input of stem cells or 'prothymocytes' is necessary to maintain T-cell development in the adult thymus, but the colonizing cell has not been characterized. Precursors of T cells have been found in the minor CD4-8- population of thymocytes, but even the earliest cells of this population already have partially rearranged T-cell antigen receptor (TCR) genes. We now demonstrate that the thymus contains a minute population of lymphoid cells similar in some but not all respects to bone marrow-derived haemopoietic stem cells. This population has TCR genes in a germline state. It gives a slow but extensive reconstitution of both alpha beta and gamma delta lineages on transfer into an irradiated thymus, with kinetics indicating that it includes the earliest intrathymic precursor cells so far isolated. Surprisingly, these cells express low surface levels of the mature T-cell marker CD4.
Strong expression of CD55 and CD59 completely protected porcine kidneys from hyperacute rejection and allowed a detailed analysis of xenograft rejection in the absence of immunosuppression. Coagulopathy appears to be a common feature of pig-to-baboon renal transplantation and represents yet another major barrier to its clinical application.
In this chapter we have summarized our view of the subsets of murine CD4- CD8- thymocytes which can be identified with a range of monoclonal antibodies. We have shown the division rate and turnover time of the main subsets and have listed what we know of the TcR gene rearrangement, and expression at the RNA and protein levels. We have been unable to completely segregate gamma delta-TcR-expressing cells from alpha beta-TcR-expressing cells by any of the markers we have used, although the proportions of the two receptor forms vary widely in the different subsets. Experiments involving intrathymic transfer of the CD4- CD8- subsets are described, which indicate that all the TcR- subsets of the CD4- CD8- thymocytes display some precursor activity and which suggest a progression of at least five stages through the TcR- subpopulations of CD4- CD8- cells. The earliest precursor is a Thy 1 low, HSA low, Pgp-1 high cell which has unrearranged C beta and is non-dividing and which closely resembles the bone marrow prothymocyte. The later precursors are Thy 1 high, HSA high, Pgp-1 low, have rearranged C beta and are rapidly dividing. We tentatively conclude that none of the TcR+ CD4- CD8- cells are precursors of the major thymocyte subsets or of typical peripheral T cells, and we have found no evidence so far of separate precursors for the different mature subsets of thymocytes or peripheral T cells.
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