Granulomatous responses of murine liver to group A streptococcal antigens

Immunogenetic studies demonstrated that susceptibility of mice to streptococcus-induced HGL was associated with the H-2{dollar}sp k{dollar} or H-2{dollar}sp b{dollar} haplotype, whereas resistance was related to the H-2{dollar}sp d{dollar} haplotype. As evidenced in H-2-congenic mice with AKR background and their F1 hybrids, susceptibility was inherited as a recessive trait. The mapping of related genes within the H-2 complex in recombinant mice with A, B10 or C3H background strongly suggested that gene or genes in and near the S region of the H-2 complex was involved. Comparative study in mice with different genetic background revealed the contribution of non-H-2-linked genes to the development of streptococcus-induced hepatic lesions. However, hepatic granuloma formation induced by group A streptococcal antigens seemed not to be related to sex in mice.; The susceptibility of C57BL/6J mice to streptococcus-induced HGL was significantly reduced by in vivo depletion of T cells. Furthermore, SCID mice and athymic nude mice, both of which lack functional T cells, failed to develop streptococcus-induced HGL. However, when both strains of immunodeficient mice were reconstituted with human peripheral blood leukocytes (huPBL), subsequent challenge with streptococcal antigens resulted in hepatic granulomatous inflammation in 71% of SCID and 80% of athymic nude mice. Successful engraftment of huPBL in immunodeficient mice was suggested by detection of human IgG in murine serum and demonstrated by in vivo tracing of H33342-labeled huPBL. FACS analysis and other immunohistologic studies demonstrated the appearance of human T cells in the murine liver and in the granulomatous lesions. All these findings illustrate that T cell are essential for the formation of S. pyogenes-induced HGL in mice and that huPBL can contribute significantly to the development of those hepatic lesions in human-mouse chimeras.; Immunobiological studies of liver non-parenchymal cells (LNPC) demonstrated for the first time that inflammatory LNPC activated by streptococcal antigens were capable of inhibiting and destroying neoplastic cells in vitro. This streptococcal antigen-induced antitumor activity was accompanied by increased influx of LNPC, higher percentage of large lymphocytes in the liver and enhanced production of IL-1 and colony-stimulating factor. The results suggest that this murine model may be useful in the analysis of bacterial antigen-LNPC interactions and of the therapeutic effects of microbial components on tumors as well as in the evaluation of the patterns of cytokine production associated with granulomatous liver disease.