Protection of Mice from Acute Graft-versus-Host Disease Requires CD28 Co-stimulation on Donor CD4⁺ Foxp3⁺ Regulatory T Cells.

ABSTRACT: Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell plus T cell transplantation (allo-HSCT). In this study, we investigated the requirement for CD28 co-stimulation of donor CD4⁺ conventional (CD4⁺CD25^-Foxp3^-, Tconv) and regulatory (CD4⁺CD25⁺Foxp3⁺, Treg) T cells in aGvHD using tamoxifen-inducible CD28 knockout (iCD28KO) or wild-type (wt) littermates as donors of CD4⁺ Tconv and Treg. In the highly inflammatory C57BL/6 into BALB/c allo-HSCT transplantation model, CD28 depletion on donor CD4⁺ Tconv reduced clinical signs of aGvHD, but did not significantly prolong survival of the recipient mice. Selective depletion of CD28

SUBMITTER: Uri A 

PROVIDER: S-EPMC5481316 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature