title: Highly conserved CDR3 region in circulating CD4(+)Vβ5(+) T cells may be associated with cytotoxic activity in Chagas disease.
abstract: Human infection with Trypanosoma cruzi leads to Chagas disease, which presents as several different clinical conditions ranging from an asymptomatic form to a severe dilated cardiomyopathy. Several studies have demonstrated that T cells play a critical role in the development of cardiac pathology, as well as in immunoregulation during chronic disease. However, the mechanisms that drive protective or pathogenic T cell response are not known. We have shown that CD4(+) T cells from chagasic patients preferentially express T cell receptor (TCR) β-chain variable region (Vβ) 5. The aim of this work was to determine whether T cells expressing this particular Vβ region displayed variable or restricted CDR3 sequences, as an indicator of the nature of the stimulus leading to the activation of these T cells in vivo. Additionally, we aimed to evaluate phenotypic characteristics of these cells that might be associated with pathology. CDR3 junctional region sequencing of Vβ5·1 expressing CD4(+) T cells revealed the occurrence of a highly homologous CDR3 region with conserved TCR Jβ region usage among patients with cardiac, but not indeterminate, Chagas disease. Moreover, correlation analysis indicated that the frequency of CD4(+)Vβ5·1(+) cells is associated with granzyme A expression, suggesting that these cells might display cytotoxic function. Together these results provide new insight into T cell recognition of antigens involved in Chagas disease and suggest that these cells may be implicated in the pathogenesis of chagasic cardiomyopathy.
authors: Department of Biological Sciences, Exact and Biological Sciences Institute, Federal University of Ouro Preto, Minas Gerais, Brazil.
authors: C A S
authors: CA
authors: Menezes
authors: A K
authors: AK
authors: Sullivan
authors: M T
authors: MT
authors: Falta
authors: D G
authors: DG
authors: Mack
authors: B M
authors: BM
authors: Freed
authors: M O C
authors: MO
authors: Rocha
authors: K J
authors: KJ
authors: Gollob
authors: A P
authors: AP
authors: Fontenot
authors: W O
authors: WO
authors: Dutra
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014355:Chagas Disease / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005786:Gene Expression Regulation / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D022801:Complementarity Determining Regions; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta