CD4-CELL-MEDIATED GRANULOMATOUS PATHOLOGY IN SCHISTOSOMIASIS IS DOWN-REGULATED BY A B-CELL-DEPENDENT MECHANISM REQUIRING FC RECEPTOR SIGNALING( T)

The effector functions of CD4(+) T lymphocytes are generally thought t o be controlled by distinct populations of regulatory T cells and thei r soluble products. The role of B cells in the regulation of CD4-depen dent host responses is less well understood. Hepatic egg granuloma for mation and fibrosis in murine schistosomiasis are dependent on CD4(+) lymphocytes, and previous studies have implicated CD8(+) T cells or cr oss-regulatory cytokines produced by T helper (Th) lymphocytes as cont rolling elements of this pathologic process. In this report, we demons trate that B cell-deficient (mu MT) mice exposed to Schistosoma manson i develop augmented tissue pathology and, more importantly, fail to un dergo the spontaneous downmodulation in disease normally observed duri ng late stages of infection. Unexpectedly, B cell deficiency did not s ignificantly alter T cell proliferative response or cause a shift in t he Th1/Th2 balance. Since schistosome-infected Fc receptor-deficient ( FcR gamma chain knockout) mice display tile same exacerbated egg patho logy as that observed in infected mu MT mice, the B cell-dependent reg ulatory mechanism revealed by these experiments appears to require rec eptor-mediated cell triggering. Together, the data demonstrate that hu moral immune response/FcR interactions can play a major role in negati vely controlling inflammatory disease induced by CD4(+) T cells.