CD4(-)CD8(-) T-cells in primary Sjögren's syndrome: association with the extent of glandular involvement.
OBJECTIVE
Growing evidence suggests that IL-17-producing T cells, lacking both CD4 and CD8 molecules and defined as double negative (DN) cells, play a pivotal role in the pathogenesis of a number of systemic autoimmune disorders. We recently demonstrated that this T-cell subset is expanded in the peripheral blood (PB) of patients with primary Sjögren's syndrome (pSS), produces IL-17 and accumulates in minor salivary glands (MSGs). We aimed to investigate glandular and PB DN T cells in early pSS in order to verify a possible correlation with MSGs histological patterns and clinical parameters.


METHODS
Paired samples of PB mononuclear cells and MSGs from pSS patients were evaluated at the diagnosis by flow cytometry and immunofluorescence staining respectively. Histological analysis to identify histological scores, B/T cell segregation and the presence of germinal center (GC)-like structures was also performed.


RESULTS
In early stages of pSS, circulating DN T cells appear to be not yet expanded and inversely correlated with circulating CD4(+)Th17 cells. The number of infiltrating DN T cells were associated with extent of glandular involvement, presence of GC-like structures and dryness symptoms and were inversely correlated with circulating DN T cells.


CONCLUSIONS
Our findings suggest that DN T cells are actively involved in the pathogenic mechanisms leading to glandular dysfunction and damage in pSS and may play a role in ectopic lymphoneogenesis development occurring during the disease.
Rheumatology Unit, Department of Medicine, University of Perugia, Via Enrico Dal Pozzo, s.n.c., Perugia I-06126, Italy. Electronic address: alessia.alunno@libero.it.
Alessia
A
Alunno
Rheumatology Unit, Clinical Science and Biotechnology Department, University of L'Aquila, Via dell'Ospedale, s.n.c., L'Aquila I-67100, Italy. Electronic address: francescocarubbi@libero.it.
Francesco
F
Carubbi
Rheumatology Unit, Department of Medicine, University of Perugia, Via Enrico Dal Pozzo, s.n.c., Perugia I-06126, Italy. Electronic address: o.bistoni@libero.it.
Onelia
O
Bistoni
Rheumatology Unit, Department of Medicine, University of Perugia, Via Enrico Dal Pozzo, s.n.c., Perugia I-06126, Italy. Electronic address: s.cater@alice.it.
Sara
S
Caterbi
Rheumatology Unit, Department of Medicine, University of Perugia, Via Enrico Dal Pozzo, s.n.c., Perugia I-06126, Italy. Electronic address: elena.bartolonibocci@unipg.it.
Elena
E
Bartoloni
Institute of Hematology, University of Perugia, S. Andrea delle Fratte, Perugia I-06132, Italy. Electronic address: bigernab@yahoo.it.
Barbara
B
Bigerna
Institute of Hematology, University of Perugia, S. Andrea delle Fratte, Perugia I-06132, Italy. Electronic address: robyriky@libero.it.
Roberta
R
Pacini
School of Environmental Sciences, University of Camerino, Via Gentile III da Varano, Macerata I-62032, Italy. Electronic address: daniela.beghelli@unicam.it.
Daniela
D
Beghelli
Rheumatology Unit, Clinical Science and Biotechnology Department, University of L'Aquila, Via dell'Ospedale, s.n.c., L'Aquila I-67100, Italy. Electronic address: paola.cipriani@cc.univaq.it.
Paola
P
Cipriani
Rheumatology Unit, Clinical Science and Biotechnology Department, University of L'Aquila, Via dell'Ospedale, s.n.c., L'Aquila I-67100, Italy. Electronic address: roberto.giacomelli@cc.univaq.it.
Roberto
R
Giacomelli
Rheumatology Unit, Department of Medicine, University of Perugia, Via Enrico Dal Pozzo, s.n.c., Perugia I-06126, Italy. Electronic address: roberto.gerli@unipg.it.
Roberto
R
Gerli
D000328:Adult; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D012470:Salivary Glands, Minor / Q000276:immunology* / Q000473:pathology*; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D015704:CD4 Antigens; D016827:CD8 Antigens
Double negative T cells; Minor salivary gland biopsy; Sjogren's syndrome; Th17 cells