Reduction of syngeneic tumor growth by an anti-I-J-alloantiserum.

Abstract

Highly significant suppression of the growth of S1509a and Sa-I syngeneic sarcomas was observed in A/J mice following daily intravenous injections of 2 ;&l of anti-I-Jk alloantiserum. This effect persisted as long as the anti-I-Jk serum was administered (day 15). In contrast, a control anti-I-Js serum had no discernible effect on the growth of the S1509a tumor. The inhibitory activity of the anti-I-k serum on the growth of the tumor was absorbed specifically by B10BR spleen cells bearing I-Jk determinants. In other experiments, we established that A/J mice treated with anti-I-Jk serum, according to the protocol described above, are no longer a source of tumor-specific suppressor cells for adoptive transfer into immune tumor-bearing recipient mice. We conclude that anti-I-Jk serum inhibits tumor growth in A/J mice by abolishing tumor-specific suppressor activity.The failure of the host to mount an effective immune response against growing syngeneic, yet demonstrably antigenic, tumors has been attributed to complex tumor and host factors that protect the tumor against the immune defenses of the host. One of the mechanisms favoring tumor growth is the development of specific suppressor thymus-derived (T) cells. Recent studies of the host reaction to murine syngeneic tumors have established that a progressively growing methylchloranthrene-induced fibrosarcoma stimulates the development, within the lymphoid organs, of T cells capable of suppressing the immune rejection of the tumor (1, 2). Furthermore, such suppressor T cells were shown to produce tumor-specific H-2 coded products with tumor-enhancing properties (3). This tumor-specific suppressor T cell factor and other specific T cell factors capable of suppressing antibody responses (4-6) or contact sensitivity (7, 8) have similar biological and immunochemical properties. Suppressor T cells (9) and specific suppressor factors (8, 10, 11) bear determinants coded for by the I-J subregion of the H-2 complex not displayed on other T cells or other immunological regulatory factors.Anti-I-J antisera could, therefore, be expected to behave as highly effective antisuppressor agents in vivo. Recent studies by Pierres et al. (12) in our laboratory have investigated the effect of anti-I-J alloantisera, administered intravenously, on the antibody response to suboptimal doses of sheep erythrocytes (SRBC). The injection of microliter quantities of anti-I-Jk antisera regularly and significantly enhanced IgM and IgG responses of A/J mice to SRBC (12). Prompted by these results, we investigated the effect of anti-I-J antisera on the growth of syngeneic methylcholanthrene-induced sarcomas S1509a and

Prognostic value of preoperative serum CEA level compared to clinical staging. I. Colorectal carcinoma

“…A possible explanation might be the influence of circulating tumour antigens on immune surveillance as -potential inducers of suppressor cells. Suppressor T cells responsive to tumour antigens prevent both the generation (Greene et al, 1977a, b) and expression (Asherson & Zembala, 1976) of T effector cells. These suppressor T cells persist after surgical removal of the tumour (Fujimoto et al, 1976) whereas the direct blocking effect of tumour antigens and its irnmune complexes against T effector cells observed with tumour-bearer sera disappears within a few days after tumour removal (Hellstr6m et al, 1970).…”

Direct evidence for loss of human suppressor cells during active autoimmune disease.

“…Adult thymectomy and administration of small doses of Cytoxan or antisera directed at the IJ subregion of the major histocompatibility complex in the mouse have also been shown to eliminate suppressor T-cell functions both in vio and in vitro (33)(34)(35). Moreover, diminished suppressor cell function was associated with both enhanced antibody formation and the capacity to generate cytotoxic cells to modified self or syngeneic tumor cells.…”

Demonstration of active tolerance in maintenance of established islet of Langerhans allografts.

“…Graft acceptance may also be prolonged if grafts depleted of passenger lymphocytes activate suppressor cells in the recipient, thus leading to a state of tolerance. Cellular (4,5) and humoral (6, 7) immunity have been shown to be regulated by antigen-specific suppressor T lymphocytes. Such suppressor cells, which express I-J determinants (8), probably inhibit both T helper cells and B cells stimulated by an antigenic challenge and lead to antigen-specific nonresponsiveness.…”

“…Such suppressor cells, which express I-J determinants (8), probably inhibit both T helper cells and B cells stimulated by an antigenic challenge and lead to antigen-specific nonresponsiveness. Suppressor cells have been shown to be important in tumor immunity (9) and in unresponsiveness to tissue allografts in mice rendered tolerant neonatally (10). Treatment of mice with specific anti-I-J sera increases primary antibody responses (11) and suppresses tumor growth (12), presumably by eliminating I-J-bearing suppressor T cells.…”

“…On day 0, an average of 211 days after transplantation, the animals were divided into five groups. Animals in group A received daily injections of anti-I-Jb serum for 36 days starting on day 1 (9) (26). This suggested that tolerance was mediated by suppressor cells in these animals.…”