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Complement-dependent lymphocytotoxic autoantibodies (CLA) are invariably present in sera of patients with active systemic lupus erythematosus (SLE). This study aimed to test for the influence of such antibodies on the in vitro generation of human alloantigen reactive proliferative and cytotoxic T cell responses. Unsensitized or alloantigen primed memory cells were pre-treated with CLA in the presence or absence of complement. Following stimulation of the remaining cells with allogeneic peripheral blood mononuclears, the proliferative and cytotoxic capacity was evaluated. Results indicated that only pre-treatment with CLA and complement influenced these reactions whereas in the absence of complement antibodies were totally ineffective. Pre-treatment of unsensitized precursor cells reduced and delayed both proliferative and cytotoxic reactivity; in contrast, pre-treatment of memory cells exclusively reduced cellular cytotoxicity. It thus appears that such SLE associated autoantibodies in the presence of complement are capable of modifying the balance between different subsets of alloreactive T cells.
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Conditions for the production of highly effective human T-cell growth factor (TCGF) and its screening in a thymidine incorporation assay are described. Culture medium supplemented with optimum concentrations of TCGF was used in bulk culture systems for the expansion of alloactivated and non-alloactivated T-cell populations. Surface marker studies of cells grown in TCGF-dependent culture showed that the majority were T cells expressing DR antigens. These cells retained their proliferative responsiveness in mixed leucocyte cultures but were unable to stimulate proliferation of normal allogeneic lymphocytes. Cultured cells which derived from mixed leucocyte cultures retained immunological specificity compared with cells not exposed to TCGF both in terms of proliferative responses caused by allogeneic cells in the absence of TCGF, and in terms of cytotoxic activity against 51Cr-labelled target cells. In addition they were capable of suppressing tritiated thymidine incorporation in mixed leucocyte cultures. These experiments show that continuous culture with TCGF can expand a variety of T-cell subpopulations with retention of distinct immunological function.
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