In vivo generation of oligoclonal colitic CD4+ T-cell lines expressing a distinct T-cell receptor Vβ

Ana C. Abadía-Molina, Atsushi Mizoguchi, William Alvis Faubion, Ype P. De Jong, Svend T. Rietdijk, Martina Comiskey, Kareem Clarke, Atul K. Bhan, Cox Terhorst

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Abstract

Background & Aims: Transplantation of wild-type (H-2k) bone marrow into tgε26 mice (BM→tgε26) 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 tgε26 recipients, starting with the population of CD4+ cells in the mesenteric lymph nodes of BM→tgε26 mice. Methods: CD4+ cells purified from the mesenteric lymph nodes of colitic BM→tgε26 mice were adoptively transferred into a second group of healthy tgε26 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 Vβ repertoire. Results: CD4+ T cells maintained a dominant T-helper 1 phenotype after multiple transfers (≤8) into recipient tgε26 mice. A single T-cell receptor Vβ was enriched (as much as 90%) in 8 CD4 + T-cell lines: Vβ8S3, Vβ8S1/2, Vβ10S1, or Vβ14. Sequence analyses of the T-cell receptor Vβs showed clonality or the presence of a very restricted number of clones within each line. Adoptive transfers of the oligoclonal lines into either C3H × Rag-/- or severe combined immunodeficiency disease mice (H-2k) also induced colitis, whereas transfers into BALB/c × 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 Vβs in each cell line responded to antigens presented by class II major histocompatibility complex.

Original languageEnglish (US)
Pages (from-to)1268-1277
Number of pages10
JournalGastroenterology
Volume128
Issue number5
DOIs
StatePublished - May 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Gastroenterology

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Abadía-Molina, A. C., Mizoguchi, A., Faubion, W. A., De Jong, Y. P., Rietdijk, S. T., Comiskey, M., Clarke, K., Bhan, A. K., & Terhorst, C. (2005). In vivo generation of oligoclonal colitic CD4+ T-cell lines expressing a distinct T-cell receptor Vβ. Gastroenterology, 128(5), 1268-1277. https://doi.org/10.1053/j.gastro.2005.01.060