Avaliação do tratamento com anticorpos monoclonais: anti-CTLA4 (9H10) e anti- CD28 (PV-1) na esquistossomose mansônica murina

Abstract

Schistosomiasis mansoni is a major problem affecting public health, according to World Health Organization (WHO), 210 million individuals worldwide. In the infected host, the disease is characterized by the presence of granuloma, immunopathological outcome of the cellular infiltrate and in many cases a consequence of tissue fibrosis. Thus, the host-parasite relationship may lead to morbidity from the disease result in hepatosplenomegaly, hepatic fibrosis and ascites. The granulomatous process in schistosomiasis is dependent on CD4 + and requires recruitment and accumulation of inflammatory cells at the site of deposition of eggs. Schistosomal fibrosis is the result of granulomatous reaction that develops in response to antigens released by eggs of Schistosoma mansoni retained in the portal veins of smaller caliber. A host of disease caused by S. mansoni is mediated by the immune response by T cells through the dissemination of eggs that are housed in the liver and intestine. Manipulation of the interaction between B7 molecules of antigen presenting cells (APC) and T cell receptors CD28/CTLA4 modulate, and in some circumstances block the immunological response in vivo. The CTLA4 is structurally homologous to CD28 but is expressed in CD4 + and CD8 + newly activated, and its function is to inhibit T cell activation by inhibiting the signals released by CD28. Thus, CTLA4 is involved in the completion of T cell responses The way in which the two receptors release opposite signs and recognize the same molecule B7 of APC is an intriguing question and a matter of research. Coestimulatory these signals may have different roles in various types of immune response. Thus the treatment strategy of using monoclonal antibodies (mAb) anti-CTLA4, anti-CD28 in murine schistosomiasis was to evaluate the modulation of inflammatory response and parasite-induced S. mansoni as CTLA4 and CD28 were blocked. Our results showed that treatment with (mAb) anti CD28 and CTLA4 molecules coestimulatory favored changes in the number of leukocytes, modulations in the levels of circulating antibodies, cytokines, and the response profile of T helper (Th) and change in the parasitic activity. Our data showed that the reduction of parasite burden was 21.3% in the group treated with anti-CTLA4 mAb and 46.2% in the group treated with anti-CD28. Suggesting that these treatments should be considered interesting candidates for immunotherapy and for further investigation, since it is necessary to better understand the response of these molecules in schistosomiasis mansoni that when blocked or did not show the hypothetical anti-parasitic and anti-inflammatory activity in this model.