Merkenschlager, Mattias Michael; (1990) Maturation stages of human T lymphocytes and distinguished by the differential expression of CD45 isoforms. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Two approximately reciprocal populations of human peripheral blood T cells express high and low molecular mass isoforms of CD45, as identified by CD45RA and CD45R0 monoclonal antibodies (mAbs). Because these populations differ in their immunoregulatory functions, they were regarded as independent sublineages. However, changes in CD45 isoform expression occur during the differentiation of hematopoietic cells, and accompany the in vitro activation of T lymphocytes. This thesis presents evidence that immunological memory is associated with the CD45R0 phenotype in CD4 and CDS T cells. Limiting dilution analysis shows high frequencies of memory dependent (recall) responses among CD45R0, but not CD45RA T cells. In contrast, both populations respond with similar frequencies to alloantigens. The response kinetics essentially rule out immunoregulatory (suppressive) phenomena as an explanation for the poor responsiveness of CD45RA T cells to recall antigens. Expression of CD45RA determinants is therefore characteristic of unprimed T cells. Constitutively expressed, lymphokine-induced, and transfected class II antigens on a variety of cell types are used to probe the repertoire and the activation requirements of these cells. In the thymus, CD45R0 is the predominant CD45 isoform expressed. The significance of differential isoform expression by thymocytes is not understood. Experiments in a recently described chimeric organ culture system indicate that loss of CD45RA expression precedes the activation- induced death of thymocytes by apoptosis. Collectively, these findings imply that the sequential expression of CD45 isoforms marks stages in thymic and post-thymic T cell maturation. This conclusion suggests a dynamic view of the immune system that allows changes in both the phenotype and the functional program of individual cells.

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