Jd. Nieland et Am. Kruisbeek, A T-CELL LYMPHOMA CAN PROVIDE POTENT COSTIMULATORY EFFECTS TO T-CELLSTHAT ARE NOT MEDIATED BY B7-1, B7-2, CD40, HSA OR CD70, International immunology, 7(11), 1995, pp. 1827-1838
Dominant second signals for T cell activation can be generated through
interactions between CD28 and CTLA-4 on T cells with their co-stimula
tory ligands B7-1 and B7-2 on APC. Nevertheless, some B7-negative cell
lines appear capable of providing second signals to T cells, illustra
ting that B7-independent co-stimulatory pathways may exist. One such c
ell line, the peptide-transporter defective T lymphoma RMA-S, was inve
stigated in the present study, to determine the origin of the co-stimu
latory effects it provides. RMA-S can support clonal expansion of puri
fied CD4 or CD8 T cells from unprimed mice activated with concanavalin
A (ConA) or immobilized anti-CD3. Nevertheless, RMA-S does not expres
s B7-1 or B7-2, nor does it express other known co-stimulatory molecul
es, i.e. CD40, gp39, CD70 and HSA. Also, co-stimulation provided by RM
A-S could not be blocked by antibodies or fusion proteins specific for
these co-stimulatory molecules, excluding their participation. Howeve
r, RMA-S' co-stimulatory activity is dependent on adhesive interaction
s. RMA-S is incapable of IL-2 production in the presence of ConA or an
ti-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 I
I-restricted T cell clones can be provided by RMA-S, and RMA-S can pre
clude induction of anergy by 1-ethyl-3-(3-dimethyl amino propyl)carboi
imide-fixed APC in a class II-restricted T cell clone. The results sug
gest that potent co-stimulatory pathways can be induced by cellular in
teractions 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.