In Vivo Generation of Oligoclonal Colitic CD4+ T-Cell Lines Expressing a Distinct T-Cell Receptor Vβ.

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. [Copyright &y& Elsevier]