ABNORMAL CD45RC EXPRESSION AND ELEVATED CD45 PROTEIN-TYROSINE-PHOSPHATASE ACTIVITY IN LEC RAT PERIPHERAL CD4(-CELLS() T)

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 p eripheral lymphoid organs, and these cells exhibit a defect in interle ukin-2 (IL-2) production upon concanavalin A (Con A) stimulation. Alth ough peripheral CD4(+) cells in normal rat highly expressed CD45RC (CD 45RC(high)), the level of CD45RC expression was low (CD45RC(low)) in L EC rat peripheral CD4(+) cells. However, CD4+ cells from both strains highly expressed CD45 when those cells were stained by pan-CD45 mAb, s uggesting 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)F-1 x LEC were examined, the phenotype for CD45 expression pattern in CD4(+) cells was clearly correlated with IL-2 production le vel in response to Con A stimulation. Thus, CD45RC(low) cells exhibit a defect in IL-2 production, while CD45RC(high) cells show normal IL-2 production. Protein tyrosine phosphatase (PTPase) activity in the mem brane fraction of LEC rat CD4(+) cells was threefold higher than that of normal rat CD4(+) cells. Con A stimulation led to an increase in ty rosine 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 res ults suggest that an elevated CD45 PTPase activity is responsive for a defect in IL-2 production in LEC rat peripheral CD4(+) T cells.