B7.1 Costimulatory Molecule Is Expressed on Thyroid Follicular Cells in Hashimoto's Thyroiditis, But Not in Graves' Disease

Abstract

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.

Association of the −31C/T functional polymorphism in the interleukin-1β gene with the intractability of Graves' disease and the proportion of T helper type 17 cells

“…On the other hand, we expected that genetic producibility of IL-1b may also relate to the severity of HD, because IL-1b induces the expression of some chemokines and surface molecules on thyrocytes in vitro and seems to enhance the inflammatory destruction of thyrocytes [35][36][37]. However, the IL-1b -31C/T polymorphism was not associated with the severity of HD (Table 1), suggesting no association between the genetic producibility of IL-1b and the severity of HD.…”

Bronchial epithelial cell B7-1 and B7-2 mRNA expression after lung transplantation: a role in allograft rejection?

“…Under normal circumstances the parenchymal donor cells lack B7 costimulatory molecules, and the indirect alloantigen presentation of the transplant recipient by professional APCs is believed to be the predominant pathway of T-cell activation in the long term after transplantation [1]. However, this concept is based mainly on experiments with rodents and does not take into account recent reports of B7 expression on human cells, which do not belong to the professional APCs, for example epithelial cells from different tissues including the lung [2][3][4][5][6]. In contrast to the expression of B7 molecules, human bronchial epithelial cells are well known to express MHC II antigens [12].…”

“…YE et al [2] reported B7-1 and B7-2 expression in a human gastric epithelial cell line as well as in isolated epithelial cells from gastric biopsies. Other types of epithelial cells with evidence of B7 expression include ductal and acinar salivary gland epithelial cells from patients with Sjoegren9s syndrome [3], biliary epithelial cells from patients suffering from primary biliary cirrhosis or primary sclerosing cholangitis [4], and thyroid follicular cells of surgically-removed thyroid tissue from patients with Hashimoto9s thyroiditis [5]. Recently, KANEKO et al [6] reported B7 expression on bronchiolar and alveolar epithelial cells.…”

A B cell explanation for autoimmune disease: the forbidden clone returns

“…T cells are likely to be on the effector side of the relationship as the T cell derived receptor activator of nuclear factor κ B ligand (RANKL) activates osteoclasts and is likely to drive bone erosion 91. In the thyroid, Battifora et al noted that intrathyroidal T cells were responsive to the B7 ligand, CD28 92. This would fit with the same B–T cell scenario driving tissue damage in the target organ as occurs in RA.…”