Role of thymic stromal lymphopoietin (TSLP) in palifermin-mediated immune modulation and protection from acute murine graft-versus-host disease.

Using the C57BL/6→(C57BL/6 x DBA/2)F(1)-hybrid model of acute graft-versus-host disease (GVHD), we previously showed that treating the donor mice with palifermin provides protection from morbidity and a shift from Th1 to Th2 cytokine production. To determine whether thymic stromal lymphopoietin (TSLP) is involved in palifermin-mediated immune modulation, we used donors from the following groups: (1) untreated wild-type donors, (2) palifermin-treated wild-type donors, (3) untreated TSLPR(-/-) donors, and (4) palifermin-treated TSLPR(-/-) donors. Survival in the recipients was 0%, 100%, 31%, and 0%, for groups 1-4, respectively, indicating that TSLP responsiveness is required for palifermin-mediated protection from GVHD. We also found that the increases in Th2 cytokine levels that are induced by palifermin treatment are obviated in TSLPR(-/-) donors, and that protection from GVHD (group 2) is associated with a higher percentage of CD4(+)CD25(+)Foxp3(+) cells in the graft. Collectively, our findings show that when palifermin and TSLP act in concert, the predominant effect is protection in this model.