Comparative studies on tumor and adjuvant (BCGcw)-induced nonspecific suppressor cells in rats.

Comparative studies on tumor and adjuvant-induced depression of in vitro mitogen responses were carried out using spleen cells obtained from syngeneic tumor bearing (TB) ACI rats or from rats which had been immunized with BCG cell walls attached to oil droplets (BCGcw). These in vitro studies demonstrated that: 1) the spleen cells from TB rats (TB-spleen cells) showed strongly depressed mitogen responses to concanavalin-A (Con-A), phytohemagglutinin-P (PHA-P) and lipopolysaccharide (LPS), 2) the mitogen response of lymph node cells from TB rats was slightly depressed, 3) the removal of plastic or nylon-wool adherent cells or phagocytic cells from TB-spleen cells resulted in a restoration of the mitogen response, 4) the Con-A response of normal spleen cells could be suppressed by the addition of TB-whole spleen cells, 5) the suppressor cell activity was not abrogated by the in vitro treatment with x-irradiation (2000 rads), 6) carbonyl-iron treated TB-spleen cells showed a normal level of mitogen response, and on addback to normal spleen cells no suppressive activity was detected in them. Similar results were observed when spleen cells were obtained from BCGcw immunized rats. These results suggest that in ACI rats tumor-induced nonspecific suppressor cells detected by in vitro assay are the same cell populations as BCGcw-induced nonspecific suppressor cells.

Negative and positive immunobiological responses in mice pretreated with Bacillus Calmette-Guérin cell wall.

Spleen cells from C57BL/6 mice injected i.p. with Bacillus Calmette-Guérin cell walls (BCGcw) showed strongly depressed response to the T-cell mitogen phytohemagglutinin-P in vitro. Mitogen reactivity of normal spleen cells could be suppressed by the addition of spleen cells from BCGcw-treated mice. The suppressor cells mediating this effect appeared to belong to the plastic-adherent, radioresistant, and non-T-cell populations, maybe macrophages. Spleen cells from mice which had been passively transferred i.p. with the adherent cells from BCGcw-treated mice also showed the depressed mitogen response in vitro. Depressed T-cell reactivity of spleen cells obtained from animals immunized with BCGcw on a per-cell basis was also demonstrated in vivo: graft versus host reactivity of spleen cells obtained from animals immunized with BCGcw was depressed as compared to normal spleen cells. At times when strong suppressor cell activity could be detected in BCGcw-treated mice, activity of alloimmune cytotoxic lymphocytes generated in vivo by immunizing with X-irradiated allogeneic MH-134 tumor cells was weaker in BCGcw-pretreated mice than in untreated control groups (detected by means of 51Cr release assay). Furthermore, accelerated development of s.c. inoculated syngeneic B-16 melanoma cells was observed in BCGcw-pretreated mice. On the other hand, stronger resistance to i.v. inoculated B-16 tumor cells was observed in BCGcw-pretreated mice. BCGcw-treated mice responded normally to i.p. immunization with 2 X 10(8) sheep erythrocytes. Negative and positive immunobiological responses were observed in C57BL/6 mice pretreated with BCGcw.