In vivo generation of oligoclonal colitic CD4+ T-cell lines expressing a distinct T-cell receptor Vbeta.
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.
Abadía-Molina
Ana C
AC
Division of Immunology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Mizoguchi
Atsushi
A
Faubion
William A
WA
De Jong
Ype P
YP
Rietdijk
Svend T
ST
Comiskey
Martina
M
Clarke
Kareem
K
Bhan
Atul K
AK
Terhorst
Cox
C
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*
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