Abnormal CD45RC expression and elevated CD45 protein tyrosine phosphatase activity in LEC rat peripheral CD4+ T cells.
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.
Sakai
T
T
Institute for Animal Experimentation, University of Tokushima School of Medicine, Japan.
Agui
T
T
Matsumoto
K
K
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D002454:Cell Differentiation; D003208:Concanavalin A / Q000494:pharmacology; D004790:Enzyme Induction; D005786:Gene Expression Regulation; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D017493:Leukocyte Common Antigens / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000235:genetics; D012326:RNA Splicing; D051381:Rats; D011916:Rats, Inbred F344; D011922:Rats, Mutant Strains
D007376:Interleukin-2; D007527:Isoenzymes; D003208:Concanavalin A; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases