CD134 expression on CD4+ T cells is associated with nephritis and disease activity in patients with systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is characterized by a deviation of the immune system that involves T cell-dependent autoantibody production. The aim of this study was to investigate the role of co-stimulatory markers on T cells in this disease. Twenty-eight patients with SLE as defined by the American College of Rheumatology (ACR) criteria and 11 healthy controls were included into the study. Eleven patients had biopsy-proven lupus nephritis while 17 patients had no clinical evidence of lupus nephritis. Clinical disease activity was assessed according to the systemic lupus erythematosus disease index (SLEDAI). CD4+ T cell populations in the peripheral blood were analysed for the expression of co-stimulatory markers CD45RO, CD70, CD80, CD86, CD137, CD137L, CD134, CD152, CD154 and ICOS. SLE patients showed an increased frequency of peripheral CD4+ T cells expressing high levels of CD80, CD86 and CD134 compared to healthy controls (7.1 +/- 1.5% versus 1.7 +/- 0.9%; P < 0.005; 2.3 +/- 0.4% versus 1.0 +/- 0.2%; P = 0.008, 20.2 +/- 2.0% versus 10.6 +/- 1.9%; P < 0.005, respectively). Significantly higher levels of CD80 on CD4+ T cells were detected in SLE patients with lupus nephritis compared to patients without nephritis (11.9 +/- 3.3% versus 4.0 +/- 0.7%; P < 0.005). There was an increased presence of CD134+ CD4+ cells in SLE patients with lupus nephritis (27.5 +/- 4.0% versus 15.5 +/- 1.3%; P < 0.005). CD80 and CD134 expression was significantly correlated with SLEDAI (r = 0.42, P = 0.03; r = 0.56, P < 0.005). Co-stimulatory molecules on CD4+ T cells are associated with renal disease and disease activity in patients with systemic lupus erythematosus.

Fig. 1

(a) Expression of co-stimulatory molecules on peripheral CD4⁺ T cells in patients with systemic lupus erythematosus (SLE) (n = 28), in patients with rheumatoid arthritis (n = 10) and healthy controls (n = 11). (b) Expression of co-stimulatory molecules on peripheral CD4⁺ T cells in SLE patients with (n = 11) and without nephritis (n = 17). The illustrated data are shown as mean values (± s.e.m.). Significant differences by the Mann–Whitney U-test are indicated: *P < 0·05; **P < 0·005.

Fig. 2

Expression of CD80, CD86 and CD134 on CD4⁺ T cells in six systemic lupus erythematosus (SLE) patients in the course of time is illustrated. The horizontal bars represent the mean percentage of CD134/CD4⁺ T cells.

Fig. 3

Correlation between the percentage of CD134 expressing CD4⁺ T cells and disease activity as measured by systemic lupus erythematosus disease index score analysed for all samples taken (n = 28).

Fig. 4

CD134 clustering was determined by fluorescence microscopy analysing 200 cells/sample. The representative microscopy images show T lymphocytes of patients with active lupus nephritis (a) versus T lymphocytes of patients without active lupus nephritis (b).