title: In vivo generation of oligoclonal colitic CD4+ T-cell lines expressing a distinct T-cell receptor Vbeta.
abstract: OBJECTIVE
  Transplantation of wild-type (H-2k) bone marrow into tg epsilon26 mice (BM-->tg epsilon26) induces colitis, characterized by T-helper cell type 1 activation in the lamina propria. Here we determined whether pathogenic T-cell clones could be derived by serial adoptive transfers into healthy tg epsilon26 recipients, starting with the population of CD4+ cells in the mesenteric lymph nodes of BM-->tg epsilon26 mice.
  
  
  METHODS
  CD4+ cells purified from the mesenteric lymph nodes of colitic BM-->tg epsilon26 mice were adoptively transferred into a second group of healthy tg epsilon26 recipients. Mesenteric lymph node CD4+ cells from the second group of mice were then used for consecutive transfers. Lamina propria CD4+ cells isolated from each mouse with colitis were analyzed for their cytokine profile and for their T-cell receptor Vbeta repertoire.
  
  
  RESULTS
  CD4+ T cells maintained a dominant T-helper 1 phenotype after multiple transfers (< or = 8) into recipient tg epsilon26 mice. A single T-cell receptor Vbeta was enriched (as much as 90%) in 8 CD4+ T-cell lines: Vbeta8S3, Vbeta8S1/2, Vbeta10S1, or Vbeta14. Sequence analyses of the T-cell receptor Vbetas showed clonality or the presence of a very restricted number of clones within each line. Adoptive transfers of the oligoclonal lines into either C3H x Rag-/- or severe combined immunodeficiency disease mice (H-2k) also induced colitis, whereas transfers into BALB/c x Rag-/- or severe combined immunodeficiency disease mice (H-2d) did not.
  
  
  CONCLUSIONS
  Colitis-inducing CD4+ T-helper 1 cell clones can be obtained by enrichment through sequential adoptive transfers of CD4+ cells from mesenteric lymph nodes. Distinct dominant T-cell receptor Vbetas in each cell line responded to antigens presented by class II major histocompatibility complex.
authors.affiliation: Division of Immunology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Abadía-Molina
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mizoguchi
authors.forename: William A
authors.initials: WA
authors.lastname: Faubion
authors.forename: Ype P
authors.initials: YP
authors.lastname: De Jong
authors.forename: Svend T
authors.initials: ST
authors.lastname: Rietdijk
authors.forename: Martina
authors.initials: M
authors.lastname: Comiskey
authors.forename: Kareem
authors.initials: K
authors.lastname: Clarke
authors.forename: Atul K
authors.initials: AK
authors.lastname: Bhan
authors.forename: Cox
authors.initials: C
authors.lastname: Terhorst
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002999:Clone Cells; D003092:Colitis / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D016513:Mice, SCID; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; C499308:Rag2 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064655:V(D)J recombination activating protein 2