Abstract
The growth of murine lymphomas carrying the H-2d (LSTRA, P388), the H-2k (6C3HED), and the H-2a (LAF-17) haplotypes was studied in spleen and liver of lethally irradiated (850 to 1000 R) ...compatible or allogeneic mice, with the 125I-5-iodo-2′-deoxy-uridine uptake method. According to the genetic pattern of the Hh (hemopoietic-histocompatibility) system, recipient hosts were either susceptible or resistant to bone marrow graft carrying the same haplotypes as those of the lymphomas studied. The results showed that the tumor cell growth was impaired in the spleen of irradiated Hh-incompatible resistant hosts (e.g., P388 into B10, B10.BR and CBA), suggesting that lymphoma and bone marrow cells could share common Hh antigens. However, inhibition of lymphoma growth occurred also in the spleen of irradiated Hh-susceptible mice, either Hh-compatible (e.g., P388 into B10.D2; 6C3HED into AKR or CBA) or Hh-incompatible, but genetically unable to respond against bone marrow cells (e.g., LSTRA or P388 into C3H, or 6C3HED into BALB/c or SJL). In almost all cases growth inhibition was absent or weak in the liver. These results suggest that lymphoma cells could express antigens not detectable on normal bone marrow cells, capable of eliciting radioresistant inhibition of tumors (RIT) predominantly in the spleen of mice susceptible to marrow graft of the same genetic origin as that of the lymphoma tested. At the present time no direct data are available to determine whether natural cytotoxicity would play a role in RIT responses.
In vitro preculture of C3H/He splenocytes for 48 to 96 hr induces aspecific suppressor cells evaluated by their ability to reduce 3H-TdR uptake by fresh syngeneic splenocytes stimulated by different ...amounts of Concanavalin A (Con A) in vitro. This suppressive activity is obtained in medium containing 10% heat-inactivated fetal calf serum (FCS) or similar amounts of heat-inactivated bovine serum, syngeneic, or allogeneic murine sera but not by unheated FCS. Suppressive activity is resistant to mitomycin C and radiation up to 5,000 R. Exposure of precultured cells to carbonyl iron or plastic adherence, but not to anti-Thy 1.2 serum plus complement, results in removal of the suppressive activity.
The immunodepressive and bone marrow stem cell-reducing activities of imidazole-4-carboxamide,5-(3,3-dimethyl-1-triazeno) (DTIC), an antitumoral agent reported to possess little immunodepressive ...capacity in man, have been investigated in mice and compared with those displayed by cyclophosphamide (Cy). In this species, single doses of DTIC could profoundly depress antilymphoma allograft resistance as well as the number of antibody-producing cells after primary and secondary stimulation with sheep erythrocytes. The highest immunodepressive activity was observed when DTIC was given before antigen and the effect observed was substantially more long lasting than seen with Cy, which was, however significantly more active on a milligram per kilogram basis. In contrast, both agents displayed a quantitatively equal activity in reducing bone marrow stem cells. It is concluded that DTIC can be an effective immunodepressant and that this activity may have clinical implications.
To explore the therapeutic potential of the thymic hormone preparation thymostimulin (TS) in animal models of cell-mediated and humoral autoimmunity, its effects were investigated on experimental ...allergic encephalomyelitis in guinea pigs and on anti-erythrocytic autoantibody production in C57B1/6 mice. In both autoimmunity models, TS produced significant therapeutic effects in terms of proportion of diseased animals, disease severity and/or disease duration; however, both the TS dose and the time of treatment start relative to the disease-inducing stimulus critically influenced results. TS effects on the generation and expression of suppressive activity induced in C57B1/6 mice by a supraoptimal immunization with 10(10) SRBC were also examined. TS given after 10(10) SRBC did not influence the level of suppression, and the activity of effectors of suppression was not modified by this agent. Conversely, using a treatment protocol analogous to that effective in reducing murine autoantibody production, TS administration prior to 10(10) SRBC was associated with a significant increase in the subsequent generation of T-dependent, antigen-specific suppressive activity. These findings suggest that effects of TS on the development of suppressor cells may be involved in the activity of this agent in animal models of autoaggression.
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