B7.1 costimulatory molecule is expressed on thyroid follicular cells in Hashimoto's thyroiditis, but not in Graves' disease.
The molecules of the B7 family play a major role in T-lymphocyte costimulation through interaction with their counterreceptors CD28 and CTLA4. In the present study, we analyzed the possible expression of B7 molecules on surgically removed thyroid tissue of patients with autoimmune [Hashimoto's thyroiditis (HT) or Graves' disease (GD)] or nonautoimmune [nontoxic goiter (NTG) or papillary cancer (PC)] thyroid diseases. We found clear positivity of thyroid follicular cells for B7.1 in HT but not in GD, nor in nonautoimmune specimens (NTG, PC) using in situ analysis by alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. Double immunostaining experiments in combination with an anti-human thyroglobulin antibody confirmed follicular B7.1 localization. On the contrary, no follicular B7.2 expression was observed in any specimen analyzed. These findings were confirmed by immunofluorescence flow cytometry on isolated follicular cells. The cytokines IL1beta and LPS were able to induce de novo B7.1 expression on cultured thyroid follicular cells. Intrathyroid T cells proved responsive to stimulation via the B7 ligand CD28, even in the absence of IL2. Moreover preliminary evidence was obtained for an inhibitory effect of anti-B7.1 mAb on T-cell proliferation in coculture with isolated thyroid follicular cells. It is conceivable that in HT, expression of B7.1 on follicular cells, together with MHC class II antigens and ICAM1, could provide a local costimulatory signal for T-lymphocyte differentiation toward the type 1 cytokine secretion pattern and maintenance of the autoimmune process.
Battifora
M
M
Allergy and Clinical Immunology Service, University of Genoa, Italy.
Pesce
G
G
Paolieri
F
F
Fiorino
N
N
Giordano
C
C
Riccio
A M
AM
Torre
G
G
Olive
D
D
Bagnasco
M
M
D000328:Adult; D000368:Aged; D018122:B7-1 Antigen / Q000032:analysis*; D018106:CD28 Antigens / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006111:Graves Disease / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013961:Thyroid Gland / Q000378:metabolism* / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000378:metabolism*
D018122:B7-1 Antigen; D018106:CD28 Antigens