Phenotypic Alterations Involved in CD8+ Treg Impairment in Systemic Sclerosis.
Systemic sclerosis (SSc) is a connective tissue disease characterized by tissue fibrosis, vasculopathy, and autoimmunity. Although the exact pathogenetic mechanisms behind SSc remain to be fully elucidated, a great deal of evidence suggests the existence of an unbalanced ratio between the effector and regulatory arms of the immune system. With regard to the T regulatory (Treg) compartment, we observed that CD8+ Treg subsets display functional defects in SSc-affected patients. Since CD127 down-modulation and CD39 upregulation have been observed on Treg subsets, the phenotypic expression of these molecules was analyzed on the CD8+CD28- Treg precursors and on CD8+ Treg cells generatedin vitrothrough interleukin-10 commitment. Immunophenotypic data from SSc patients were compared to those obtained from healthy subjects. The analyses performed onex vivo-isolated CD8+CD28- Treg precursors did not show any significant differences in CD39 or CD127 expression as compared to values obtained from healthy donors. On the contrary,in vitro-generated CD8+ Tregs obtained from SSc patients displayed reduced expression of the CD39 molecule as compared to controls. Moreover, the percentage of CD127+ cells was significantly higher inin vitro-generated CD8+ Tregs from SSc patients compared to CD8+ Tregs obtained from healthy donors. Taken together, these findings may indicate an impairment of maturation processes affecting CD8+ Treg cells in SSc patients. This impairment of maturation involves phenotypic alterations that are mainly characterized by a deficient CD39 upregulation and a lack of down-modulation of the CD127 molecule.
Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy; Department of Internal Medicine, Clinical Immunology Unit, University of Genoa, Genoa, Italy.
Simone
S
Negrini
Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy; Department of Internal Medicine, Clinical Immunology Unit, University of Genoa, Genoa, Italy.
Daniela
D
Fenoglio
Center of Excellence for Biomedical Research, University of Genoa , Genoa , Italy.
Alessia
A
Parodi
Center of Excellence for Biomedical Research, University of Genoa , Genoa , Italy.
Francesca
F
Kalli
Center of Excellence for Biomedical Research, University of Genoa , Genoa , Italy.
Florinda
F
Battaglia
Center of Excellence for Biomedical Research, University of Genoa , Genoa , Italy.
Giorgia
G
Nasi
Center of Excellence for Biomedical Research, University of Genoa , Genoa , Italy.
Monica
M
Curto
Center of Excellence for Biomedical Research, University of Genoa , Genoa , Italy.
Samuele
S
Tardito
Center of Excellence for Biomedical Research, University of Genoa , Genoa , Italy.
Francesca
F
Ferrera
Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy; Department of Internal Medicine, Clinical Immunology Unit, University of Genoa, Genoa, Italy.
Gilberto
G
Filaci
CD127; CD39; CD8+ T regulatory cells; scleroderma; systemic sclerosis