Chinn, Deborah Louise; (1997) The examination of minimal requirements for proliferative responses to alloantigen by naive and memory T cells, defined by the leukocyte common antigen isoforms. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Murine transfected fibroblast cell lines (TFCL) expressing HLA-DR1 (DR1) alone or co transfected with CD58 or CD54 were used as allostimulators to investigate the minimal triggering requirements for CD45R subset allogeneic proliferation. Whole PBMC and CD45R subsets gave weak alloresponses to DR1+TFCL. The proportion of responders was greater for PBMC than either of the CD45 subsets. Stronger alloresponses by PBMC and CD45R subsets against DR1+CD54 and DR1+CD58 TFCL were observed. Generally, CD45RA+ and CD45RO+ T cell subsets alone gave weaker alloresponses than whole PBMC. Recombining purified CD4+ CD45R subsets after separation, led to responses similar in magnitude to whole PBMC, implying that the reconstitution of CD45R subsets has a co-operative effect mediated through either physical contact or cytokines. Alloresponses by PBMC and CD4 CD45R populations to TFCL and LCL were all increased by the addition of IL-2. CD45RA+ T cell responses to TFCL and LCL were significantly enhanced by the presence of IL-4, whereas in comparison, CD45RO+T cells and not CD45RA+ alloresponses were augmented by the addition of IFN?. Whole PBMCs primed with DR1+TFCL that normally produce low levels of proliferation induced vigorous responses when rechallenged with either DR1+LCL or DR1+TFCL. This is a strong indication that HLA-DR expressed on the TFCL is recognised by the responder T cell despite reduced primary alloresponses. The addition of autologous monocytes or CD28 MAbs to alloresponses involving TFCL or LCL increased proliferative responses by both CD4+CD45RA+ and CD4+CD45RO+ T cells.

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