Functional characterization of infiltrating T lymphocytes in human hepatic allografts

Abstract

We have employed recently developed techniques in T-cell culturing to study the nature and function of infiltrating hepatic allograft T cells. Using the rationale that intragraft T cells are activated during cell mediated damage to the allograft, we were able to show that these cells would propagate and remain functionally active in the presence of the T-cell growth factor, IL-2. In several instances, phenotypic analysis of cells grown in this manner was very similar to that found within the graft. Both proliferative and cytotoxic responses could be detected from the cultured cell lines. The majority of the proliferative responses were donor-directed and immunogenetic analysis could define donor-directed HLA reactivity, to either class I or class II antigens, or both. Monoclonal anti-HLA antibodies inhibition profiles verified the apparent HLA reactivity. In a smaller percentage of cases, only IL-2 responsiveness could be detected, and no HLA reactivity could be determined. Cytotoxicity could be detected against both class I and class II antigens, however, those cells which demonstrated a greater magnitude of donor-directed cytotoxicity appeared to be directed against class I antigens. A significant correlation between donor-directed proliferation of biopsy cultured lymphocytes and cellular rejection was found. This model appears to be useful in delineating functions of the intragraft T-cell population during rejection.

Pathologic analysis of liver transplantation for primary biliary cirrhosis

“…Functional a~alysis of.graftinfiltrating lymphocytes cultured from lIver sp.ecIm~ns during a rejection reaction have confirmed prolIferative and cytotoxic activity directed at these antigens (18).…”

Sensitivity of activated human lymphocytes to cyclosporine and its metabolites

“…Alloreactive lymphocyte cultures were also propagated from human heart and liver core biopsies in the presence of IL-2 as previously reported (2,3]. Secondary proliferation of alloreaccive cells was assessed in a 3-day primed lymphocyte test (PLT), whereby 10 4 responder cells were incubated with 10 1 irradiated (2000 R) stimulator cells [12].…”

“…T cells from transplanted tissues have demonstrated the presence of donorspecific lymphocytes in transplanted organs at various stages of rejection [1][2][3]. Donor-specific T cells have also been grown from transplant biopsies without any evidence of an ongoing or pending rejection episode as diagnosed clinically or histologically [4}.…”

Human leukocyte antigen–C in short- and long-term liver graft acceptance

“…1,3 In liver transplantation, studies about the impact of HLA antigens have given contradictory results. 1,[4][5][6] However, there is evidence that HLA antigens are involved in cellular immune responses, 7,8 and that a high HLA class I expression, as well as specific HLA class II alleles, such as DQB1*0302, may be related to liver graft tolerance and rejection. 9,10 In regard to HLA-matching, previous studies reported that a total class I mismatch in combination with partial or complete class II match has lead to vanishing bile duct syndrome.…”