The role of accessory cells in polyclonal T cell activation III. No requirement for recognition of H‐2‐encoded antigens on accessory cells

Abstract

Highly purified murine lymph node T cells were used to test the hypothesis that polyclonal T cell activation requires the recognition of mitogen-modified major histocompatibility complex (MHC) antigens on accessory cells (AC) by the T cells. A variety of tumor cells lines, including macrophage, B and mast cell tumors, as well as thymomas, were shown to function as AC in concanavalin A-induced T cell activation, even if they expressed only one class of MHC antigens or none at all. In contrast to antigen-specific responses, where the Lyt-2+ phenotype is reportedly associated with recognition of class I MHC antigens, T cells enriched for or depleted of Lyt-2+ cells were not preferentially activated in the presence of class I- or class II-positive AC, respectively. In addition, as shown by others in the guinea pig and in the rat systems, T cell proliferation induced by oxidation of cell surface sugars is equally effective if T cells or AC are oxidized. T cell mitogens, therefore, do not seem to act by altering MHC antigens on AC, but rather by providing T cell-AC contact via their agglutinating properties.

Costimulatory signal provided by a B-lymphoblastoid cell line and its Ia-negative variant.

“…An analysis of T-cell activation mediated by the lectin Con A or by stimulatory mAbs against the Thy-1 molecule or against the CD3 component of the T-cell antigen receptor complex hereby gave qualitatively similar results. Our results are consistent with previous experiments by Hunig (42) and by Malek et al (43), who have shown that several murine Ia-negative cell lines, including a fibroblastoid cell line and a T-cell tumor, can provide a costimulatory function, although the basis for this phenomenon was not defined. We have taken these experiments one step further by actually comparing an Ia-negative variant cell line to its wild-type parent and by demonstrating that the metabolically fixed B cell lines M12 and M12.C3 can also provide accessory cell function.…”

B-cell-stimulatory factor 2 (beta 2 interferon) functions as a second signal for interleukin 2 production by mature murine T cells.

“…Although IL-1 has been reported to be a sufficient second signal for IL-2 production, we and others (7,(15)(16)(17)(18) have found that exogenous IL-1 does not restore the response of purified murine T cells to Con A or to anti-T cell receptor antibodies. These results contrast with two recent reports showing that recombinant IL-1 restored the proliferative response of purified human T cells stimulated with immobilized antibodies directed against the T3/T-cell receptor complex (33,34).…”

“…Previous studies (10,11) have shown that either ofthese reagents can stimulate purified T cells to respond to exogenous IL-2 but not to produce IL-2. Despite the well-entrenched notion that the cytokine interleukin-1 (IL-1) is a sufficient second signal for IL-2 production (12)(13)(14), a variety of recent reports have failed to demonstrate IL-2 production by purified T cells stimulated with IL-1/Con A (6,7,(15)(16)(17)(18).…”

T cell stimulation by staphylococcal enterotoxins. Clonally variable response and requirement for major histocompatibility complex class II molecules on accessory or target cells.

“…A proposed mechanism for T cell activation by mitogenic lectins is the crosslinking of the TCR complex (17,18) or CD2 (19) with glycoproteins on the AC surface. The presence of MHC molecules on the AC is not required (8,20). As an alternative hypothesis, it has been suggested that polyclonal T cell activation, in some cases, may be due to an immunological recognition of mitogen-modified MHC molecules (21) .…”