BIASED LIVER T-CELL RECEPTOR V-BETA REPERTOIRE IN A MURINE GRAFT-VERSUS-HOST DISEASE-MODEL

Murine graft-vs-host disease (GVHD) results in destruction of small bi le ducts in the liver. We analyzed the TCR V beta repertoire of lympho cytes isolated from the livers and spleens of individual B10.D2 into i rradiated BALB/c GVHD mice by means of two-color immunofluorescence. E ach mouse showed an increase in at least one V beta population in the liver and spleen, but the expanded V beta populations were heterogeneo us and variable among individual GVHD mice. Overall, the repertoire of liver CD4 cells was biased toward V beta 2 and 3 expression with 65 a nd 88% of mice, respectively, showing an increase in these subsets. Th e splenic CD4 cell repertoire was biased toward V beta 3 and 4 express ion (50% of mice each). The repertoire of CD8 cells was less biased wi th 20 to 35% of mice showing expansions of V beta 3(+), 4(+), 5(+), 6( +), 8.1(+), 8.2(+), and 8.3(+) T cells in both the liver and spleen. V beta 2(+) CD4 cells were increased preferentially in the liver compar ed with the spleen. These results indicate that the infiltrating liver and splenic T cells are polyclonal and suggest that donor T cells rec ognize multiple host non-MHC Ags in this GVHD model. Alloantigens reco gnized by V beta 2(+) CD4 cells appear to be selective for the liver; Expansion of V beta 3(+) CD4 cells may reflect recognition of the host Mls-3 superantigen.