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A T4+ proliferative, noncytotoxic cloned line acquires specific lytic function by treatment with recombinant interferon alpha or gamma. Simultaneous with the acquisition of this new cell function, a rearrangement of the T-cell receptor alpha gene occurs. These changes necessitate a revised concept of a T-cell clone regarding its T-cell receptor gene configuration and cell function.

Allostimulated T lymphocytes were cloned by micromanipulation and expanded in IL-2 conditioned medium. Three T3+,T4+,T8-, clones called BJ1, BJ4, and BJ37, were extensively studied. The BJ1 cells were able to proliferate and kill the specific target. The BJ4 and BJ37 cells were able to proliferate with the specific restimulator but could not kill even in lectin-dependent cell-mediated cytotoxic assay; however, they acquired the specific cytolytic activity in the 6-day culture when fresh irradiated autologous peripheral blood mononuclear cells as feeder cells were added to the specific irradiated Epstein-Barr virus transformed cell line, in the presence of recombinant IL-2. This observation strongly suggested that the culture conditions could be involved in the differentiation of proliferative clones into cytotoxic T lymphocyte (CTL) clones, by the lymphokines, either present in the IL-2 conditioned medium or secreted by the mixed allogeneic irradiated feeder cells. Moreover, it was shown that the acquisition of the cytolytic function could be blocked by the monoclonal antibody LeoA1, previously described and which recognized the TLiSA1 structure involved in the CTL differentiation.

Cells from two siblings within family PER with a maternal crossing-over were used as responder and stimulator cells; they differed in class II MHC gene products. The responder cells were cloned and studied for their specificity. All the clones were T4+, most of them, were allospecific cytotoxic T-cell clones, some were only proliferative. Among the 62 clones that have been screened for their phenotype and function, we could expand, in our cloning system, two autoreactive T-cell clones specific for the self-class II MHC products. The results indicated that this autoreactivity was also observed in serum-free medium, which excludes any serum components susceptible to alter the self-class II MHC products. For the autorecognition, the two clones used the T3-Ti complex, and only one of them, the T4 structure.