CD4+ T cell-mediated granulomatous pathology in schistosomiasis is downregulated by a B cell-dependent mechanism requiring Fc receptor signaling

Dragana Jankovic, Allen W. Cheever, Marika C. Kullberg, Thomas A. Wynn, George Yap, Patricia Caspar, Fred A. Lewis, Raphael Clynes, Jeffrey V. Ravetch, Alan Sher

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Abstract

The effector functions of CD4+ T lymphocytes are generally thought to be controlled by distinct populations of regulatory T cells and their soluble products. The role of B cells in the regulation of CD4-dependent host responses is less well understood. Hepatic egg granuloma formation and fibrosis in murine schistosomiasis are dependent on CD4+ lymphocytes, and previous studies have implicated CD8+ T cells or cross-regulatory cytokines produced by T helper (Th) lymphocytes as controlling elements of this pathologic process. In this report, we demonstrate that B cell-deficient (μMT) mice exposed to Schistosoma mansoni develop augmented tissue pathology and, more importantly, fail to undergo the spontaneous downmodulation in disease normally observed during late stages of infection. Unexpectedly, B cell deficiency did not significantly alter T cell proliferative response or cause a shift in the Th1/Th2 balance. Since schistosome-infected Fc receptor- deficient (FcR γ chain knockout) mice display the same exacerbated egg pathology as that observed in infected μMT mice, the B cell-dependent regulatory mechanism revealed by these experiments appears to require receptor-mediated cell triggering. Together, the data demonstrate that humoral immune response/FcR interactions can play a major role in negatively controlling inflammatory disease induced by CD4+ T cells.

Original languageEnglish (US)
Pages (from-to)619-629
Number of pages11
JournalJournal of Experimental Medicine
Volume187
Issue number4
DOIs
StatePublished - Feb 16 1998

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Jankovic, D., Cheever, A. W., Kullberg, M. C., Wynn, T. A., Yap, G., Caspar, P., Lewis, F. A., Clynes, R., Ravetch, J. V., & Sher, A. (1998). CD4+ T cell-mediated granulomatous pathology in schistosomiasis is downregulated by a B cell-dependent mechanism requiring Fc receptor signaling. Journal of Experimental Medicine, 187(4), 619-629. https://doi.org/10.1084/jem.187.4.619