[Glucocorticoid induced TNFR-related protein (GITR) as marker of human regulatory T cells: expansion of the GITR(+)CD25⁻ cell subset in patients with systemic lupus erythematosus].

Abstract

OBJECTIVES:

Regulatory T cells (T(REG)) represent a T cell subset able to modulate immune response by suppressing autoreactive T-lymphocytes. The evidence of a reduced number and an impaired function of this cell population in autoimmune/inflammatory chronic diseases led to the hypothesis of its involvement in the pathogenesis of these disorders. Glucocorticoid-induced TNFR-related protein (GITR) is a well known marker of murine T(REG) cells, but little is known in humans. The aim of this study was to investigate the characteristics of T(REG) cells in systemic lupus erythematosus (SLE) and the potential role of GITR as marker of human T(REG).

METHODS:

Nineteen SLE patients and 15 sex- and age-matched normal controls (NC) were enrolled. CD4(+) T cells were magnetic sorted from peripheral blood by negative selection. Cell phenotype was analyzed through flow-cytometry using primary and secondary antibodies and real time polymerase-chain reaction (PCR) using TaqMan probes.

RESULTS:

The CD25(high)GITR(high) subset was significantly decreased in SLE patients with respect to NC (0.37±0.21% vs 0.72±0.19%; p<0.05). On the opposite, the CD25⁻GITR(high) cell population was expanded in the peripheral blood of SLE patients (3.5±2.25 vs 0.70±0.32%, p<0.01). Interestingly, FoxP3 at mRNA level was expressed in both CD25⁻GITR(high) and CD25(high)GITR(high) cells, suggesting that both cell subsets have regulatory activity.

CONCLUSIONS:

CD4(+)CD25⁻GITR(high) cells are increased in SLE as compared to NC. The expression of high level of GITR, but not CD25, on FoxP3+ cells appears to point to a regulatory phenotype of this peculiar T cell subset.

• Authors: A Alunno, G Nocentini, O Bistoni, R Bianchini, E Bartoloni Bocci, C Riccardi, R Gerli
• Journal: Reumatismo (Reumatismo) 2010 Jul-Sep Vol. 62 Issue 3 Pg. 195-201 ISSN: 0048-7449 [Print] Italy
• Vernacular Title: Glucocorticoid-induced TNFR-related protein (GITR) come marker di cellule T regolatorie umane: espansione della sottopopolazione cellulare GITR(+)CD25⁻ in pazienti affetti da lupus eritematoso sistemico.
• PMID: 21052566 (Publication Type: English Abstract, Journal Article)

Chemical References

• Antigens, Differentiation, T-Lymphocyte
• FOXP3 protein, human
• Forkhead Transcription Factors
• Glucocorticoid-Induced TNFR-Related Protein
• IL2RA protein, human
• Interleukin-2 Receptor alpha Subunit
• Receptors, Nerve Growth Factor
• Receptors, Tumor Necrosis Factor
• TNFRSF18 protein, human

Topics

• Adult
• Antigens, Differentiation, T-Lymphocyte (analysis)
• Female
• Forkhead Transcription Factors (biosynthesis)
• Glucocorticoid-Induced TNFR-Related Protein
• Humans
• Immunophenotyping
• Interleukin-2 Receptor alpha Subunit (analysis)
• Lupus Erythematosus, Systemic (blood, immunology)
• Lymphocyte Activation
• Lymphocyte Count
• Male
• Middle Aged
• Receptors, Nerve Growth Factor (analysis)
• Receptors, Tumor Necrosis Factor (analysis)
• T-Lymphocyte Subsets (chemistry, immunology, metabolism)
• T-Lymphocytes, Regulatory (chemistry, immunology, metabolism)
• Young Adult