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Allospecific T cell clones acquire the cytotoxic effector function after three months in culture in IL-2 conditioned medium
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Annual AACHT Meeting, 1985 time of rejection, tn five of six recipients of T lymphocyte depleted HLA nonidentical marrow grafts, rejection was associated with the early development of host derived T lymphocytes which were phenotypically homogeneous-and specifically cytotoxic for donor leukocytes. In two patients, the cytotoxic activity of these cells was demonstrated to be specific for a single donor HLA antigen, tn contrast, host cells developing in patients rejecting HLA identical T cell depleted marrow were more heterogeneous and exhibited a broad cytotoxic reactivity which was not specific for donor HLA antigens but which was more consistent with the reactivity of natural killer or lymphokine activated killer cells.
ABSTRACT DISCUSSION SESSION VIII: MECHANISMS OF T CELL ACTIVATION ALLOSPECIFIC T CELL CLONES ACQUIRE THE CYTOTOXIC EFFECTOR FUNCTION AFTER THREE MONTHS IN CULTURE IN IL-2 CONDITIONED MEDIUM. L.K. Chen, M. Sasportes, and A. Bensussan; Inserm U 93, H~pital St. Louis 2, Place du Dr. Fournier, 75475 Patti Cedex 10, France Allostimulated T lymphocytes were cloned by micromanipulation and maintained in culture in IL-2 conditioned medium. We selected one T cell clone, which in a lectin dependent as well as in a standard cell-mediated lymphosis assay, was not able to kill. Although the T4 phenotype and HLA-DR7 allospecificity of the cells were not modified during 3 months in culture, they acquired the cytotoxic T lymphocyte function and were then able to kill the specific and allogeneic HLADR7 unrelated targets. Moreover, the CTL effector function could be inhibited by incubating the cells overnight with the Leu-4 monoclonal antibody prior to the CML assay. The inhibition of killing was associated with the loss of T3 molecule expression shown by indirect immunofluorescence using a cytofluorograph. The relevance of such a CTL effector function acquirement is under investigation since we kept cells frozen at different times in culture, with and without the CTL function. In particular, it has been shown whether recombinant IL-2 could induce differentiation and acquirement of the CTL function. An anticlonotypic monoclonal antibody is being developed to prove the clonality of such T cells.
INDUCTION OF TOLERANCE TO EXOGENOUS ANTIBODY AMPLIFIESTHE ANALO~ GOUS CELLULARIMMUNE RESPONSE AGAINST THE ANTIGEN TO WHICH THE ANTIBODY IS DIRECTED. Richard J. Sharpe, Robert T. Schweizer, and Laurine M. Bow; Hartford Hospital, Surgical Research, Hartford, CT We attempted to enhance the immune response to an antigen in a specific fashion by inducing tolerance to exogenous antibody directed against the same antigen. The theoretical basis for this technique follows from Jerne's network theory (Ann Immunol (Paris) 125C:373, !974) of the immune system. By tolerizing the host to immunogtobulin-bearing idi0types directed against an antigen it should be possible to dampen the expected antMdiotype response to these idiotypes. Re: duction of the anti-idiotype response should result in an increased host endogenous idiotype response against the antigen. The increased idiotype response can
Annual AACHT Meeting, 1985 time of rejection, tn five of six recipients of T lymphocyte depleted HLA nonidentical marrow grafts, rejection was associated with the early development of host derived T lymphocytes which were phenotypically homogeneous-and specifically cytotoxic for donor leukocytes. In two patients, the cytotoxic activity of these cells was demonstrated to be specific for a single donor HLA antigen, tn contrast, host cells developing in patients rejecting HLA identical T cell depleted marrow were more heterogeneous and exhibited a broad cytotoxic reactivity which was not specific for donor HLA antigens but which was more consistent with the reactivity of natural killer or lymphokine activated killer cells.
ABSTRACT DISCUSSION SESSION VIII: MECHANISMS OF T CELL ACTIVATION ALLOSPECIFIC T CELL CLONES ACQUIRE THE CYTOTOXIC EFFECTOR FUNCTION AFTER THREE MONTHS IN CULTURE IN IL-2 CONDITIONED MEDIUM. L.K. Chen, M. Sasportes, and A. Bensussan; Inserm U 93, H~pital St. Louis 2, Place du Dr. Fournier, 75475 Patti Cedex 10, France Allostimulated T lymphocytes were cloned by micromanipulation and maintained in culture in IL-2 conditioned medium. We selected one T cell clone, which in a lectin dependent as well as in a standard cell-mediated lymphosis assay, was not able to kill. Although the T4 phenotype and HLA-DR7 allospecificity of the cells were not modified during 3 months in culture, they acquired the cytotoxic T lymphocyte function and were then able to kill the specific and allogeneic HLADR7 unrelated targets. Moreover, the CTL effector function could be inhibited by incubating the cells overnight with the Leu-4 monoclonal antibody prior to the CML assay. The inhibition of killing was associated with the loss of T3 molecule expression shown by indirect immunofluorescence using a cytofluorograph. The relevance of such a CTL effector function acquirement is under investigation since we kept cells frozen at different times in culture, with and without the CTL function. In particular, it has been shown whether recombinant IL-2 could induce differentiation and acquirement of the CTL function. An anticlonotypic monoclonal antibody is being developed to prove the clonality of such T cells.
INDUCTION OF TOLERANCE TO EXOGENOUS ANTIBODY AMPLIFIESTHE ANALO~ GOUS CELLULARIMMUNE RESPONSE AGAINST THE ANTIGEN TO WHICH THE ANTIBODY IS DIRECTED. Richard J. Sharpe, Robert T. Schweizer, and Laurine M. Bow; Hartford Hospital, Surgical Research, Hartford, CT We attempted to enhance the immune response to an antigen in a specific fashion by inducing tolerance to exogenous antibody directed against the same antigen. The theoretical basis for this technique follows from Jerne's network theory (Ann Immunol (Paris) 125C:373, !974) of the immune system. By tolerizing the host to immunogtobulin-bearing idi0types directed against an antigen it should be possible to dampen the expected antMdiotype response to these idiotypes. Re: duction of the anti-idiotype response should result in an increased host endogenous idiotype response against the antigen. The increased idiotype response can