T cell receptor repertoire in B cell lymphoproliferative lesions in primary Sjögren's syndrome.
OBJECTIVE
Studies have analyzed T cell receptor (TCR)-Vbeta in benign, minor salivary or lacrimal gland, or kidney lesions in Sjögren's syndrome (SS). We investigated SS related lymphoproliferative lesions.


METHODS
By "family" reverse transcriptase polymerase chain reaction, we studied the expression of 20 different TCR-Vbeta families in parotid lymphoproliferative lesions and peripheral blood lymphocytes (PBL) from 7 patients with primary SS, in PBL from 6 primary SS patients with no associated lymphoproliferative disorder, and in activated PBL from 2 healthy controls. T cell clonal expansion was investigated in 10 Vbeta families (i.e., the most expanded ones and those previously implicated in SS pathogenesis) by single strand conformation polymorphism (SSCP) analysis. Frozen sections from parotid gland specimens were tested by immunohistochemistry for the expansion of selected Vbeta families. Viral infection within the parotid lesions and serum autoantibody response were also studied.


RESULTS
An unrestricted Vbeta pattern was observed. The most widely expressed Vbeta family in parotid lesions was Vbeta2, and Vbeta immunohistochemistry results were concordant with Vbeta mRNA findings. A similar pattern was observed in PBL, although the Vbeta2 family was expressed at lower levels. The parotid/PBL ratio was occasionally > 1.8-2.0 (indicative of local Vbeta overexpression) in different Vbeta families. T cell expansion proved to be largely polyclonal by SSCP analysis, and scattered T cell clonotypes were detected within different Vbeta families, with a different pattern from patient to patient.


CONCLUSIONS
Our observations in SS related lymphoproliferative lesions largely reflect previous evidence in fully benign lesions. The pathogenetic events involved in autoimmune benign lesions in SS may then persist and play a role in SS related lymphoproliferative disorders. The link between the observed TCR-Vbeta repertoire and specific local triggering (auto)antigens remains to be elucidated.
Pivetta
B
B
Division of Experimental Oncology 1, Centro di Riferimento Oncologico, Aviano (PN), Italy.
De Vita
S
S
Ferraccioli
G
G
De Re
V
V
Gloghini
A
A
Marzotto
A
A
Caruso
G
G
Dolcetti
R
R
Bartoli
E
E
Carbone
A
A
Boiocchi
M
M
D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008223:Lymphoma / Q000209:etiology / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000276:immunology*; D008875:Middle Aged; D010305:Parotid Diseases / Q000209:etiology / Q000276:immunology* / Q000473:pathology / Q000821:virology; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis* / Q000235:genetics; D012859:Sjogren's Syndrome / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014777:Virus Diseases / Q000209:etiology / Q000821:virology
D016693:Receptors, Antigen, T-Cell, alpha-beta