Generation of T cells with differential responses to alloantigens in CD45 exon 6-deficient mice

Abstract

We characterized the CD45+ population in the CD45 exon 6-deficient mice and addressed a question as to whether the T cells keep responsive properties to alloantigens. The peripheral CD45+ T cells from the untreated knockout mice showed a decreased expression level of CD45 but increased expression levels of LFA-1α and CD44, indicating that the T cells are possibly in an activation state. The CD45 exon 6-deficient mice could readily reject fully allogeneic skin grafts but not non-MHC-disparate skin grafts. The skin allograft-rejected CD45 exon 6-deficient mice showed an increased number of peripheral CD8+ T cells expressing an isoform of CD45RB (CD45ζ). In vitro assays including mixed lymphocyte reaction, CTL, and cytokine productions were consistent to the in vivo results. Furthermore, the effector cells shown in these assays were CD45+CD8+ T cells expressing a CD45RB isoform, CD45ζ. Moreover, the CD45+ T cells had an abnormal regulation of CD45 expression level, as they could not increase their CD45 expression level after in vitro allogeneic stimulation. These results indicate that abnormal mature T cells in the periphery of CD45 exon 6-deficient mice cannot respond to nominal Ags presented by MHC but can react to allo-MHC. The reason that such functionally impaired T cells can be generated in the mice is still unknown but these results imply that there is differential requirement of CD45 function for alloreactive T cells in a thymic selection(s) and in effector functions.