Anti-L3T4 antibody treatment suppresses hepatic granuloma formation and abrogates antigen-induced interleukin-2 production in Schistosoma mansoni infection

Abstract

In murine schistosomiasis mansoni, granulomatous inflammation is an immune response that involves egg antigen presentation to T cells in the context of class II major histocompatibility complex determinants and subsequent inflammatory lymphokine production by delayed-hypersensitivity (TDH) lymphocytes. In the present study, monoclonal antibodies directed against L3T4, I-A, and Lyt-2 molecules were injected intraperitoneally into S. mansoni-infected mice to study the role of these membrane antigens in the process of granuloma formation. A dramatic suppression of the hepatic granuloma size and antigen-induced interleukin-2 (IL-2) production by spleen cells was seen in mice that received anti-L3T4 monoclonal antibody treatment. The total number of cells, especially the L3T4+ T cells, was greatly diminished in the spleens. Furthermore, histopathological study of the granulomas in stained liver sections demonstrated the paucity of eosinophils and macrophages, absence of epithelioid cells and multinucleated giant cells, and minimal collagen deposition within the lesions. Damaged hepatocytes were also seen surrounding these il-formed granulomas. In contrast, anti-I-A monoclonal antibody treatment partially suppressed IL-2 production, although granuloma size and cellular composition remained the same. Mice that received anti-Lyt-2 monoclonal antibody did not show any changes in either IL-2 production or hepatic granulomatous inflammation. The data presented in this paper indicate a crucial role for L3T4 molecules present on a subset of class II major histocompatibility complex-restricted TDH cells in IL-2 production and the generation of the granulomatous response.

Immunopathology of schistosomiasis

“…T-cell-deficient mice, in particular CD4 helper T-cell-deficient mice fail to mount an effective granulomatous response. [12][13][14] In immunocompetent wildtype (Wt) mice, immune responses to schistosome antigens manifest a striking shift from a moderate Th1 to a robust Th2-dominated response with the onset of egg laying around 5-6 weeks. 1 Whereas the relative contribution of interferon (IFN)-g-producing Th1 cells and IL-4, IL-5 and IL-13 producing Th2 cells in the granulomatous response has long been debated, fibrosis and much of the pathology is primarily mediated by Th2 cytokines 15,16 and not by transforming growth factor (TGF)-b.…”

Role for CTLA‐4 but not CD25+ T cells during Schistosoma mansoni infection of mice

“…An obligate role for T cells in schistosome granuloma formation was initially shown using various mice with T cell deficiencies (4)(5)(6). More recent studies have demonstrated that granuloma formation around the schistosome egg is dependent on CD4 + , and not on CD8 + , T cells (7)(8)(9)(10).…”

Schistosoma mansoni in Mice: the Pattern of Primary Cercarial Exposure Determines Whether a Secondary Infection Post‐chemotherapy Elicits a T Helper 1‐ or a T Helper 2‐Associated Immune Response

“…The schistosome egg granuloma is a CD4 T-cell-mediated delayed type hypersensitivity reaction [3]. CD4 T cells are functionally divisible into T helper 1 (Th1) and T helper 2 (Th2) subsets [4] and the speci®c role of each of these two components of the immune system and their associated cytokines in schistosomiasis has been the subject of intense study [5,6].…”