Modulation of Schistosoma japonicum Pulmonary Egg Granulomas with Monoclonal Antibodies

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  • Veterans Administration Medical Center and the Department of Microbiology and General Biology, Vanderbilt University, Nashiville, Tennessee 37203

We have examined the ability of various Schistosoma japonicum egg antigens to sensitize mice for subsequent secondary pulmonary egg granuloma formation. Further, we produced monoclonal antibodies (Mabs) specific for egg antigens and evaluated their abilities to modulate pulmonary granuloma formation and inhibit soluble egg antigen (SEA)-stimulated lymphocyte blastogenesis. A homogenous, 140 Kd egg glycoprotein, SJe; 140-GP was nearly as effective as intact eggs in sensitizing for egg-focused pulmonary granuloma formation, while SEA, or the heterogenous immunoaffinity (IA)-purified C10 antigens were ineffective. The in vivo administration of chronic infection serum (CIS) or Mabs reactive with SJe;140-GP, to egg-sensitized/egg-challenged mice, modulated pulmonary granuloma formation. Two of these modulatory SJe;140-GP-specific Mabs (1A1-1 or 14B3-8), an IgG1, and an IgG3, respectively, did not alter the responses of SEA-stimulated lymph node cells from mice with acute or chronic schistosomiasis japonica. In contrast, another SJe;140-GP-specific IgG3 Mab (7A6-5), CIS, immunoaffinity purified anti-SEA from CIS, or the non-SEA-binding fraction of CIS, all resulted in dose-related inhibition of SEA-induced proliferation. These data confirm the antibody-driven nature of some immunoregulatory networks in murine schistosomiasis japonica, and extend these observations to include certain Mabs. The immunogenic nature of SJe;140-GP, and the modulatory and inhibitory activities of Mabs specific for this glycoprotein, indicate it may play a central role in granuloma formation and modulation in this infection.