title: Increased CD4+/CD8+ double-positive T cells in chronic Chagasic patients.
abstract: BACKGROUND
  CD4+/CD8+ double positive (DP) T cells have been described in healthy individuals as well as in patients with autoimmune and chronic infectious diseases. In chronic viral infections, this cell subset has effector memory phenotype and displays antigen specificity. No previous studies of double positive T cells in parasite infections have been carried out.
  
  
  RESULTS
  Seventeen chronic chagasic patients (7 asymptomatic and 10 symptomatic) and 24 non-infected donors, including 12 healthy and 12 with non-chagasic cardiomyopathy donors were analyzed. Peripheral blood was stained for CD3, CD4, CD8, HLA-DR and CD38, and lymphocytes for intracellular perforin. Antigen specificity was assessed using HLA*A2 tetramers loaded with T. cruzi K1 or influenza virus epitopes. Surface expression of CD107 and intracellular IFN-γ production were determined in K1-specific DP T cells from 11 chagasic donors. Heart tissue from a chronic chagasic patient was stained for both CD8 and CD4 by immunochemistry. Chagasic patients showed higher frequencies of DP T cells (2.1% ± 0.9) compared with healthy (1.1% ± 0.5) and non-chagasic cardiomyopathy (1.2% ± 0.4) donors. DP T cells from Chagasic patients also expressed more HLA-DR, CD38 and perforin and had higher frequencies of T. cruzi K1-specific cells. IFN-γ production in K1-specific cells was higher in asymptomatic patients after polyclonal stimulation, while these cells tended to degranulate more in symptomatic donors. Immunochemistry revealed that double positive T cells infiltrate the cardiac tissue of a chagasic donor.
  
  
  CONCLUSIONS
  Chagasic patients have higher percentages of circulating double positive T cells expressing activation markers, potential effector molecules and greater class I antigenic specificity against T. cruzi. Although K1 tetramer positive DP T cell produced little IFN-γ, they displayed degranulation activity that was increased in symptomatic patients. Moreover, K1-specific DP T cells can migrate to the heart tissue.
authors: Grupo de Ciencias Básicas Médicas, Facultad de Medicina, Universidad de los Andes, Bogotá, Colombia.
authors: Nicolas A
authors: NA
authors: Giraldo
authors: Natalia I
authors: NI
authors: Bolaños
authors: Adriana
authors: A
authors: Cuellar
authors: Fanny
authors: F
authors: Guzman
authors: Ana Maria
authors: AM
authors: Uribe
authors: Astrid
authors: A
authors: Bedoya
authors: Natalia
authors: N
authors: Olaya
authors: Zulma M
authors: ZM
authors: Cucunubá
authors: Nubia
authors: N
authors: Roa
authors: Fernando
authors: F
authors: Rosas
authors: Víctor
authors: V
authors: Velasco
authors: Concepción J
authors: CJ
authors: Puerta
authors: John M
authors: JM
authors: González
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D002598:Chagas Cardiomyopathy / Q000276:immunology* / Q000473:pathology; D005260:Female; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D054353:Perforin / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D006680:HLA Antigens; D054353:Perforin; D007371:Interferon-gamma