CD45.1/CD45.2 congenic markers induce a selective bias for CD8+ T cells during adoptive lymphocyte proliferation in lymphocytopenia mice

Abstract

Abstract CD45.1/CD45.2 congenic markers have been frequently used to track hematopoietic lineage differentiation following hematopoietic stem and progenitor cell (HPSC) transplantation. However, several studies suggest that a bias exists in CD45.1 versus CD45.2 hematopoietic cell reconstitution from the transplanted HPSCs. Meanwhile, no definitive comparison has been reported for mature immune cells as to whether the CD45.1/CD45.2 disparity can skew immune cell response. In this study using lymphocytopenia Rag1−/− CD45.2 mice as hosts, we assessed the proliferative potential of CD45.1 versus CD45.2 lymphocytes following adoptive transfer of mature T and B cells harvested from the spleens of CD45.1 and CD45.2 mice. We have found that a selective bias for CD8+ T cells in that CD45.1 CD8+ T cells showed significantly higher proliferation and higher expression of PD-1 compared CD45.2 CD8+ T cells in the Rag1−/− CD45.2 hosts. This bias is likely due to MHC-I restricted allogeneic stimulation as CD45.1 versus CD45.2 CD4+ T cells and CD19+ B cells contained the same graft as CD8+ T cells showed equivalent proliferation. These results suggest that CD45.1/CD45.2 markers induce an alloreactive response specific to CD8+ T cells, and therefore call for caution for using them as congenic markers in immunologic models. This study was supported by funds through the National Cancer Institute (R01CA184728), the Maryland Department of Health's Cigarette Restitution Fund (CRF) Program and used shared core facilities supported by University of Maryland Greenebaum Comprehensive Cancer Center (UMGCC) Support Grant (P30CA134274).