Functional maturation of recent thymic emigrants in the periphery: Development of alloreactivity correlates with the cyclic expression of CD45RC isoforms
✍ Scribed by Chun-Ping Yang; Eric B. Bell
- Publisher
- John Wiley and Sons
- Year
- 1992
- Tongue
- English
- Weight
- 944 KB
- Volume
- 22
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Functional maturation of recent thymic emigrants in the periphery: development of alloreactivity correlates with the cyclic expression of CD45RC isoforms*
The transition from fully developed CD4+CD8-single-positive (SP) thymocytes into fully mature recirculating peripheral T cells is both poorly understood with regard to the expression of restricted isoforms (CD45R) of the leukocyte common antigen and in terms of T cell function. The present investigation monitored the extrathymic development of CD4+CD8-SP thymocytes in euthymic recipients using allotype-marked donor cells and monoclonal antibody OX22 which recognizes an epitope on the C exon of rat CD45R. We established that donor-derived cells in the blood 1 day later bore the phenotype of the injected SP thymocytes (CD4+ Thy-l+ CD45RC-). Tcells with the identical phenotype were also present in the thoracic duct lymph of uninjected rats, suggesting that the Thy-l+ CD45RC-T cells represent recent thymic emigrants (RTE) which have migrated to the periphery of their own accord. During extrathymic maturation donor-derived peripheral RTE lost Thy-1 within 3 days and expressed the CD45RCf high molecular weight isoform by day 7; between days 8 and 14 a proportion (25%-30%) of the donor cells once again lost the high molecular weight isoform (CD45RC). The transition of SP (CD45RC) thymocytes to fully mature CD45RCf CD4 T cells via intermediate peripheral RTE was accompanied at each stage by an increased ability of the maturingT cells to induce skin allograft rejection. Unexpectedly, the subsequent loss of the high molecular weight isoform, following presumed antigen encounter, was associated with a significant reduction in the ability of thisThy-1-CD45RC-subpopulation to effect graft rejection. The cyclic expression of CD45RC isoforms on both immature and mature CD4 Tcells and the fact that the low molecular weight isoform was found in the periphery on both RTE (unquestionably naive) and antigen-experienced CD4 T cells, makes it unlikely that this isoform uniquely identifies memory Tcells, at least in the rat.