[Anti-cytomegalovirus T-cell immunity and HLA restriction in the transplanted kidney patient]
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B Charpentier1, S Michelson, O Lantz
1Laboratoire de Transplantation d'Organes, Hôpital de Bicêtre, Kremlin-Bicêtre.
Cytomegalovirus (CMV)-specific immune T-cells, present in the circulation of previously infected kidney transplant recipients (anti-CMV serum antibody titer greater than 1/40) can be reactivated to give rise to specific helper and cytotoxic effector cells by co-culturation with fresh autologous blasts coated with CMV antigen in vitro. The reactivated cells are able: 1) to proliferate when stimulated with CMV antigen, 2) to kill the autologous target coated with CMV antigen and not autologous blasts alone when assayed in 51Cr release test. These specific effector cells lie in the E+ T cell subset by removing NK cells with sheep-erythrocytes rosetting. When the reactivated cells are tested against allogeneic CMV coated blasts the level of cytotoxicity is in general related to the extent of HLA-A and B antigen sharing between effector and target cells. The results provide strong evidence that: 1) only previously infected individuals can generate immune T cells against CMV in vitro, 2) there is a correlation between the index of proliferation and cytolysis, 3) there is an HLA restriction of immune T cell cytotoxicity of CMV, 4) monoclonal antibodies directed at several antigenic sites of CMV are able to block cytolysis.
Cytomegalovirus (CMV)-specific immune T-cells, present in the circulation of previously infected kidney transplant recipients (anti-CMV serum antibody titer greater than 1/40) can be reactivated to give rise to specific helper and cytotoxic effector cells by co-culturation with fresh autologous blasts coated with CMV antigen in vitro. The reactivated cells are able: 1) to proliferate when stimulated with CMV antigen, 2) to kill the autologous target coated with CMV antigen and not autologous blasts alone when assayed in 51Cr release test. These specific effector cells lie in the E+ T cell subset by removing NK cells with sheep-erythrocytes rosetting. When the reactivated cells are tested against allogeneic CMV coated blasts the level of cytotoxicity is in general related to the extent of HLA-A and B antigen sharing between effector and target cells. The results provide strong evidence that: 1) only previously infected individuals can generate immune T cells against CMV in vitro, 2) there is a correlation between the index of proliferation and cytolysis, 3) there is an HLA restriction of immune T cell cytotoxicity of CMV, 4) monoclonal antibodies directed at several antigenic sites of CMV are able to block cytolysis.