Biased liver T cell receptor V β repertoire in a murine graft-versus-host disease model

Abstract

Murine graft-vs-host disease (GVHD) results in destruction of small bile ducts in the liver. We analyzed the TCR V β repertoire of lymphocytes isolated from the livers and spleens of individual B10.D2 into irradiated BALB/c GVHD mice by means of two-color immunofluorescence. Each mouse showed an increase in at least one V β population in the liver and spleen, but the expanded V β populations were heterogeneous and variable among individual GVHD mice. Overall, the repertoire of liver CD4 cells was biased toward V β 2 and 3 expression with 65 and 88% of mice, respectively, showing an increase in these subsets. The splenic CD4 cell repertoire was biased toward V β 3 and 4 expression (50% of mice each). The repertoire of CD8 cells was less biased with 20 to 35% of mice showing expansions of V β 3+, 4+, 5+, 6+, 8.1+, 8.2+, and 8.3+ T cells in both the liver and spleen. V β 2+ CD4 cells were increased preferentially in the liver compared with the spleen. These results indicate that the infiltrating liver and splenic T cells are polyclonal and suggest that donor T cells recognize multiple host non-MHC Ags in this GVHD model. Alloantigens recognized by V β 2+ CD4 cells appear to be selective for the liver. Expansion of V β 3+ CD4 cells may reflect recognition of the host Mls-3 superantigen.