Basis for defective proliferation of peripheral blood T cells to anti-CD2 antibodies in primary Sjögren's syndrome.
Anti-CD2-induced T cell proliferation was analyzed in the peripheral blood samples of 31 primary and 8 secondary untreated Sjögren's syndrome patients. Anti-CD2-stimulated PBMC proliferation was very low in about one-third of primary Sjögren's syndrome samples, despite the number of CD2+ cells being similar in primary and secondary Sjögren's syndrome and normal PBMC samples. The depressed response to anti-CD2 was mainly found in anti-Ro+/La+ patients. Experiments on purified T cells demonstrated that a defect at the T cell level was responsible for the anti-CD2 unresponsiveness. Cell proliferation failure was associated with poor IL-2 and IL-2 receptor mRNA expression and, consequently, IL-2 and IL-2 receptor synthesis. Since defective anti-CD2-induced mitogenesis could be reversed by phorbol myristate acetate, but not calcium ionophore A23187, it is probably correlated with impaired protein kinase C activation. Comparison of anti-CD2-triggered PBMC proliferation in treated and untreated patients and a long-term study of nine patients showed that the defect is a stable characteristic in primary Sjögren's syndrome patients, but that it can be reversed by pharmacological immunosuppression.
Gerli
R
R
Institute of Internal Medicine, University of Perugia, Italy.
Bertotto
A
A
Agea
E
E
Lanfrancone
L
L
Cernetti
C
C
Spinozzi
F
F
Rambotti
P
P
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018801:CD2 Antigens; D000001:Calcimycin / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D007375:Interleukin-1; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate