Normal Lyt-1+2- T cells have the unique capacity to respond to syngeneic autoreactive T cells. Demonstration of a T cell network.

In the present communication, we describe the unique observation that Lyt-1+2-, L3T4+ T cells but not Lyt-2+ T cells isolated from the spleens of normal, unimmunized H-2d mice proliferate strongly and directly to an irradiated, syngeneic, Lyt-1+2-, L3T4+, Ia- autoreactive T cell line/clone. In contrast, Lyt-1+2- T cells failed to proliferate when stimulated by long-term, antigen-specific, H-2d-restricted T cell lines. Supernatants from the cultures of autoreactive T cells or recombinant interleukin 2 (IL-2) alone, failed to induce proliferation of the Lyt-1+2- T cells, suggesting that cell-cell interaction is essential for growth. In addition, the proliferative response of Lyt-1+2- T cells was independent of Ia+ antigen-presenting cells and was not blocked by either anti-Iad or anti-H-2d antibodies, but was inhibited by anti-L3T4 antibodies. All these observations suggested that the responding Lyt-1+2- T cells were recognizing the anti-self-Ia receptor expressed on autoreactive T cells and that such T cells might therefore express the internal image of self-Ia determinants. We suggest that the T-T interactions observed may represent interactions between two helper T cell subpopulations at the idiotope level and that autoreactive T cells may function as an important feature of the regulatory network and/or lead to the expansion of the T cell repertoire.