Abnormal CD45RC expression and elevated CD45 protein tyrosine phosphatase activity in LEC rat peripheral CD4+ T cells

Abstract

LEC rats are known to show a maturational arrest in the development of CD4+8+ to CD4+8- cells in the thymus. Despite the blockade of maturation of CD4+8-thymocytes, CD4+ T cells were observed in peripheral lymphoid organs, and these cells exhibit a defect in interleukin-2 (IL-2) production upon concanavalin A (Con A) stimulation. Although peripheral CD4+ cells in normal rat highly expressed CD45RC (CD45RChigh), the level of CD45RC expression was low (CD45RClow) in LEC rat peripheral CD4+ cells. However, CD4+ cells from both strains highly expressed CD45 when those cells were stained by pan-CD45 mAb, suggesting that LEC rat CD4+ cells are deficient in expression of the CD45RC isoform, but not of CD45 molecules. When backcross rats from (F344 x LEC)F1 x LEC were examined, the phenotype for CD45 expression pattern in CD4+ cells was clearly correlated with IL-2 production level in response to Con A stimulation. Thus, CD45RClow cells exhibit a defect in IL-2 production, while CD45RChigh cells show normal IL-2 production. Protein tyrosine phosphatase (PTPase) activity in the membrane fraction of LEC rat CD4+ cells was threefold higher than that of normal rat CD4+ cells. Con A stimulation led to an increase in tyrosine phosphorylation levels, especially 100- and 40-kDa proteins, in normal rat CD4+ cells. In LEC rat CD4+ cells, however, the level of tyrosine phosphorylation in those proteins were very low. These results suggest that an elevated CD45 PTPase activity is responsive for a defect in IL-2 production in LEC rat peripheral CD4+ T cells.