Adoptive immunotherapy of murine lymphosarcoma: comparative study using allo-immune or tumor-immune T cells.

The antitumor effect of allosensitization with lymphocytes and skin graft of DBA/2 mice was evaluated using immunogeneic, transplantable Lymphosarcoma (LS-A) syngeneic to Swiss mice. A dose dependent tumor inhibitory effect in terms of tumor free mice was observed in mice sensitized i.p. with lymphocyte doses between 10-100 million per animal. Sensitization with allogeneic primary skin graft was more effective than lymphocyte immunization. The antitumor immunity could be adoptively transferred in syngeneic Swiss mice using either allo-immune or tumor-immune T cells. Analysis of T cell phenotypes using monoclonal antibodies against cell surface markers CD4 and CD8, indicated absolute dependence on the CD4+ T cells subset in tumor cure in case of allo-immune as well as tumor-immune T cells. CD8+ T cell subset was found essential only in case of allo-immune T cell therapy. Immunosuppression of mice with whole body gamma irradiation (4 Gy), 6 hr before transfer of allo-immune or tumor-immune T cells did not abrogate the therapeutic ability of allo-immune or tumor-immune T cells. Our results suggest that allosensitization could be an effective method of generating effector lymphocyte populations that might be used to treat tumors that exhibit detectable immunogenecity.

Anti tubercular treatment induced hepatotoxicity: does acetylator status matter?

Anti tubercular drug related hepatotoxicity is common. The mechanism of injury and factors predisposing to its development are not fully understood. Forty patients with anti tubercular drugs related hepatotoxicity were studied to see the clinical and biochemical profile of these patients and to find out the significance of acetylator phenotype in the development of hepatotoxicity. Mean age of patients with liver damage (37.82 +/- 10.0 years) was similar to those without liver damage (36.48 +/- 12.5 years). Pyrazinamide appeared to increase the hepatotoxicity of isoniazid and rifampicin. The percentage of rapid acetylators and slow acetylators among patients with hepatotoxicity (70% and 30% respectively) was similar to controls (66.6% rapid and 33.3% slow acetylators). Acetylator phenotype probably has no role in anti tubercular drugs induced hepatotoxicity.

Effect of multigeneration alcohol feeding on murine immune system.

Mice belonging to F8, F12, F14 and F20 generation of a multigeneration study reared on 20% (v/v) ethanol in water as the sole drinking source were investigated for their immune competence using various parameters. The results indicated lack of any significant effect on delayed type hypersensitivity to dinitro fluorobenzene (DNFB) or sheep red blood cells (SRBC) in mice consuming ethanol. Further, alloskin graft and tumor graft response was similar in both ethanol and water fed mice. Humoral response to SRBC was also intact. However, NK cell activity was reduced significantly in ethanol fed mice. Phagocytic index as assessed by the carbon clearance test was also reduced considerably in mice consuming ethanol. The results clearly indicate that ethanol per se has a significant effect on the nonspecific limb of the immune system, in chronically fed mice.

Allosensitization induced suppression of various murine tumors: role of non-H-2 antigens in antitumor immunity.

Presence of alloantigens on various murine tumors was tested by tumor rejection in allosensitized Swiss mice. The results indicated the presence of alloantigen on immunogenic tumors like chemically induced fibrosarcoma (FS), ascitic sarcoma 180 (S 180) and immunogenic variant of lymphosarcoma (LS-A) in Swiss mice, while these antigens could not be detected by this procedure on spontaneous lymphosarcoma (LS). Allosensitization with skin graft was found to offer quantitatively higher antitumor resistance than the allosensitization achieved by allogeneic lymphocytes. Antitumor effect was not seen when tumor cells were inoculated earlier than day 3 of grafting. Further, host immunosuppression with whole body irradiation up to day of 3 of skin grafting abrogated the antitumor effect. H-2 compatible and non-H-2 incompatible skin graft sensitization of host could offer resistance against both S 180 and LS-A. Further, tumor immune mice rejected H-2 compatible, non-H-2 incompatible skin graft significantly earlier.