Reduced protein tyrosine phosphatase (PTPase) activity of CD45 on peripheral blood lymphocytes in patients with systemic lupus erythematosus (SLE)

Abstract

SUMMARYTo disclose the mechanism of aberrant function of peripheral blood lymphocytes (PBL) in SLE, we focused on the catalytic function of CD45, and determined the CD45 PTPase activity in SLE patients. The sample population consisted of 32 SLE patients with different disease activity. PTPase activity of cell lysates immunoprecipitated by anti-CD45 MoAb was assayed against phosphotyrosine analogue PNPP, followed by measuring the release of para-nitro phenol at 410 nm. CD45 PTPase activity of PBL was significantly decreased in SLE patients, compared with that of normal controls and patients with systemic sclerosis (964 Ϯ 265, 1202 Ϯ 172, 1210 Ϯ 125, respectively; SLE versus normal, P < 0 . 05). It was correlated with SLE Disease Activity Index (SLEDAI) score (r ¼ 0 . 597, P ¼ 0 . 0006), but not with the dose of prednisolone (r ¼ 0 . 214, P ¼ 0 . 2657), indicating that CD45 PTPase activity became reduced when the disease was active, but it was not affected by prednisolone. Moreover, it was not corrected by in vitro culture with or without stimulation. The expression of CD45 on PBL was comparable between normal and SLE, raising a possibility that it may be due to aberrant regulation of catalytic function of CD45 in SLE. Given the evidence that tyrosine phosphorylation of cellular proteins by tyrosine kinases and phosphatases is one of the key biochemical events in the signal transduction pathway, the decreased CD45 PTPase activity in SLE may account for the defective signal transduction via TCR/CD3, leading to dysregulated effector function of the lymphocytes.

Novel role for galectin-1 in T-cells under physiological and pathological conditions

“…Although there was no clear correlation between disease activity index scores or particular symptoms and Gal-1 levels, we hypothesized that low expression and diminished responsiveness of activated SLE T-cells to Gal-1 might contribute to immune regulatory dysfunction and enhanced T-cell activity in SLE pathology [17,29,34,35]. This assumption was supported by the finding that successful immunosuppressive therapy resulted in restoration of the level of Gal-1 as well as of the apoptotic sensitivity of SLE T-cells.…”

Protein phosphatase 2A is a negative regulator of IL-2 production in patients with systemic lupus erythematosus

“…Nevertheless, no abnormalities of the expression and function of these phosphatases have been demonstrated in patients with SLE. On the other hand, CD45, a transmembrane tyrosine phosphatase, which has been implicated in the molecular aberrations in SLE (83,84), exerts diverse effects on IL-2 production (75,(85)(86)(87). In particular, T cell lines that do not express cell surface CD45 cannot generate TCR signals (86) and thus cannot produce IL-2, while coligation of CD45 with the antigen receptor inhibits IL-2 production (87).…”

Signaling in human lupus T lymphocytes

“…Not surprisingly, reduced CD45 PTPase activity was described in T cells from SLE patients and was inversely correlated with disease activity. 23 It was not corrected by in-vitro culture or stimulation with PHA, and expression of the CD45RA isoform, a marker of naive T cells, was signi®cantly decreased.…”