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Enhanced proliferative response of CD4+ T cells from patients with systemic lupus erythematosus by T-cell receptor stimulation

Objective

To investigate the expression of the chemokine receptor CCR7, which defines distinct subsets of naive and memory T lymphocytes with different homing and effector capacities, and the proliferative capacity of CD4+ T cells by T-cell receptor (TCR) stimulation in patients with systemic lupus erythematosus (SLE)

Methods

Heparinized venous blood from SLE patients (23–53 years old; mean, 36.7 years) and age-matched and sex-matched healthy controls (HC) was collected. Peripheral blood mononuclear cells (PBMC) were freshly isolated by Ficoll-Hypaque. We stained 106 PBMC with anti-human CCR7 antibody, anti-CD45RA, anti-CD4 and anti-CD8 to characterize the phenotype of T-cell subsets. PBMC were stimulated with anti-CD3 + anti-CD28 monoclonal antibody, and cell division was analyzed by carboxyfluorescein diacetate succinimidyl ester labeling and flow cytometry in different subsets of CD4+ T cells. Data was acquired on a FACS caliber system, and analyzed using Flow-Jo software (Tree Star Inc., San Carlos, CA, USA).

Results

SLE patients (n = 27) had fewer CD45RA+CCR7+CD4+ naive T cells (32.2 ± 13.2 vs 43.5 ± 12.3, P < 0.05) and higher CD45RA-CCR7-CD4+ effector memory T cells (20.1 ± 12.2 vs 12.9 ± 5.6, P < 0.05) as compared with the HC (n = 27). No significant differences were found in the CD45RA-CCR7+ central memory CD4+ T cells and the CD8+ T-cell compartment of SLE patients as compared with HC. The appearance of cell division was more rapid in the population of CD45RA-CCR7-CD4+ T cells, and the frequency of CD45RA-CCR7-CD4+ effector memory T cells did not correlate with disease activity, disease duration, age, or treatment within the SLE group. Enhanced cell division was observed in SLE CD4+ T cells by TCR stimulation as compared with HC, but there are no significant correlations between frequency of effector CD4+ T cells and proliferative capacity within the SLE group. Furthermore, naive CD4+ T cells from SLE patients showed increased proliferative capacity compared with that of HC, but the difference was no so significant.

Conclusion

These results suggest that enhanced proliferative response of CD4+ T cells of SLE by TCR stimulation may be caused by increased distribution of the effector memory population and intrinsic defects of SLE CD4+ T cells.

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Keywords

  • Systemic Lupus Erythematosus
  • Peripheral Blood Mononuclear Cell
  • Systemic Lupus Erythematosus Patient
  • Effector Memory
  • Proliferative Capacity