CD4+ TCR Repertoire Heterogeneity inSchistosoma mansoni-Induced Granulomas

Abstract

The hallmark of Schistosoma mansoni infection is the formation of liver granulomas around deposited ova. The initiation of granuloma formation is T cell-dependent since granulomas are not formed in their absence. We investigated whether a few T cells arrive to initiate the inflammatory lesion and subsequently expand locally, or whether a large repertoire of systemically activated T cells home to the delayed type hypersensitivity reaction induced by the ova. The TCR repertoire of single granulomas from the same liver were analyzed by PCR using Vβ-specific primers and CDR3 analysis. Each granuloma has a very diverse TCR repertoire indicating that most of the T cells recruited to these lesions are activated systemically. At the same time, sequence analysis of individually sized CDR3 products from single granuloma indicate that a fraction of T cells expand locally at the lesion site. Using TCR transgenic mice containing a pigeon cytochrome c-specific T cell population or lymphocytic choriomeningitis virus infection tracked with lymphocytic choriomeningitis virus-specific tetramers, we demonstrated that nonspecific T cells home to the granuloma if they are activated. However, recombinase-activating gene 2−/− pigeon cytochrome c-specific TCR transgenic mice fail to form granulomas in response to S. mansoni ova even after T cell activation, suggesting a requirement for egg-specific T cells in the initiation of these inflammatory lesions. Understanding the mechanism of T cell recruitment into granulomas has important implications for the rational design of immunotherapies for granulomatous diseases.

Severe Sepsis Exacerbates Cell-Mediated Immunity in the Lung Due to an Altered Dendritic Cell Cytokine Profile

“…mansoni egg-induced granulomas require the efficient and sequential recruitment of a series of immune effecter cells, including macrophages, 36 CD4 ϩ T cells, 37 and eosinophils. 38 These specific immune cells form a strong cellular barrier and sequester the S. mansoni eggs from the surrounding healthy tissue.…”

Hepatic stereology of schistosomiasis mansoni infected-mice fed a high-fat diet

“…Obesity is also predictive of the presence of fibrosis, potentially progressing to advanced liver disease (Festi et al 2004). Schistosomiasis mansoni infection also promotes liver injury in both humans and mice yet a granulomatous inflammation is formed around mature egg (Hogan et al 2002, Stavitsky 2004). In the former, liver dysfunction, dyslipidemia, and protein alteration are common findings (Lima et al 1998).…”

Histological study on the possible therapeutic role of bone marrow derived mesenchymal stem cells in a model of Schistosoma mansoni infestation of spleen of mice

“…This was in accordance with our results as there was a significant increase in area % of collagen fibers in the granulomatous reaction surrounding a degenerated egg. According to the opinion of Hogan et al [32] TNF-α is a highly pleiotropic cytokine, with extensive biological effects. It enhances the function of antigen presenting cells, and activates monocytes.…”