A T cell lymphoma can provide potent co-stimulatory effects to T cells that are not mediated by B7-1, B7-2, CD40, HSA or CD70.

Dominant second signals for T cell activation can be generated through interactions between CD28 and CTLA-4 on T cells with their co-stimulatory ligands B7-1 and B7-2 on APC. Nevertheless, some B7-negative cell lines appear capable of providing second signals to T cells, illustrating that B7-independent co-stimulatory pathways may exist. One such cell line, the peptide-transporter defective T lymphoma RMA-S, was investigated in the present study, to determine the origin of the co-stimulatory effects it provides. RMA-S can support clonal expansion of purified CD4 or CD8 T cells from unprimed mice activated with concanavalin A (ConA) or immobilized anti-CD3. Nevertheless, RMA-S does not express B7-1 or B7-2, nor does it express other known co-stimulatory molecules, i.e. CD40, gp39, CD70 and HSA. Also, co-stimulation provided by RMA-S could not be blocked by antibodies or fusion proteins specific for these co-stimulatory molecules, excluding their participation. However, RMA-S' co-stimulatory activity is dependent on adhesive interactions. RMA-S is incapable of IL-2 production in the presence of ConA or anti-CD3, but T cells co-stimulated by RMA-S produce IL-2 and IFN-gamma upon anti-CD3- or ConA-induced activation. Furthermore, co-stimulation of antigen-specific T cell proliferation of both class I- and class II-restricted T cell clones can be provided by RMA-S, and RMA-S can preclude induction of anergy by 1-ethyl-3-(3-dimethyl amino propyl)carboiimide-fixed APC in a class II-restricted T cell clone. The results suggest that potent co-stimulatory pathways can be induced by cellular interactions between a T lymphoma, RMA-S and T cells, not involving gp39, CD40, CD70, HSA, B7-1 (CD80) or B7-2 (CD86). Characterization of the molecules involved is in progress.