Analysis of orbital T cells in thyroid-associated ophthalmopathy

Forster, G; Otto, Edgar A.; Hansen, C.; Ochs, K; Kahaly, George J.

doi:10.1046/j.1365-2249.1998.00613.x

Cited by 78 publications

(39 citation statements)

References 43 publications

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“…Although the percentage of CD4 + T cells was only significantly higher in patients with hyperthyroid GD the percentage of its subset expressing ICAM-1 was considerably increased in GO group. In agreement with that, the subset of CD4 + T cells was found to predominate in the orbit infiltration in GO [16,17]. After antigen recognition, CD4 + T lymphocytes could secrete cytokines that amplify the immune reaction by either activating CD8 + T lymphocytes or autoantibody-producing B cells [18].…”

Section: Figsupporting

confidence: 81%

Increased percentage of L-selectin+ and ICAM-1+ peripheral blood CD4+/CD8+ T cells in active Graves' ophthalmopathy.

Pawłowski

Myśliwiec²,

Stasiak-Barmuta³

et al. 2009

Folia Histochem Cytobiol.

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Abstract:The purpose of the study was to evaluate the percentage of CD4 + /CD8 + peripheral T cells expressing CD62L + and CD54 + in patients with Graves' disease and to assess if these estimations could be helpful as markers of active ophthalmopathy. The study was carried out in 25 patients with Graves' disease (GD) divided into 3 groups: 1/ 8 patients with active Graves' ophthalmopathy (GO) (CAS 3-6, GO complaints ≤1 year), 2/ 9 patients with hyperthyroid GD without symptoms of ophthalmopathy (GDtox) and 3/ 8 patients with euthyroid GD with no GO symptoms (GDeu). The control group consisted of 15 healthy volunteers age and sex matched to groups 1-3. The expression of lymphocyte adhesion molecules was evaluated by using three-color flow cytometry. In GO group the percentage of CD8 +CD54+ , CD8 +CD62L+ , CD4 +CD54+ and CD4 +CD62L+ T cells was significantly higher as compared to controls (p<0.001, p<0.05, p<0.01, p<0.001 respectively). In addition, the percentage of CD8 +CD54+ T lymphocytes was elevated in GO group in comparison to hyperthyroid GD patients (p< 0.05). CD4 +CD62L+ and CD8 +CD54+ percentages were also increased in GDtox and GDeu as compared to controls. We found a positive correlation between the TSHRab concentration and the percentage of CD8 +CD62L+ T cells in all studied groups (r= 0.39, p<0.05) and between the TSHRab level and CAS (r= 0.77, p<0.05). The increased percentage of CD8 +CD54+ and CD8 +CD62L+ T cells in patients with Graves' ophthalmopathy may be used as a marker of active orbital inflammation.

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Section: Figsupporting

confidence: 81%

Increased percentage of L-selectin+ and ICAM-1+ peripheral blood CD4+/CD8+ T cells in active Graves' ophthalmopathy.

Pawłowski

Myśliwiec²,

Stasiak-Barmuta³

et al. 2009

Folia Histochem Cytobiol.

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“…We have demonstrated that the percentage of CD8 -/IFN-Á + T cells and the ratio of CD8 -/IFN-Á + T (Th1) cells to CD8 -/IL-4 + T (Th2) cells were markedly higher in early GO patients than in GD patients and the healthy individuals, indicating that the balance of Th1/Th2 shifts to Th1 dominance in early GO (1,2). CD4 + /IFN-Á + T cells secrete IFN-Á which represents Th1-type cytokines, while CD4 + /IL-4 + T cells secrete IL-4 representing Th2-type cytokines (5).…”

Section: Discussionmentioning

confidence: 99%

“…It is believed that factors such as genes, autoimmunity, alteration of orbital fibroblast activity, environmental factors and smoking are intimately correlated to the pathogenesis of GO. The CD3 + CD4 + CD8 -T lymphocytes are predominant in the T cells derived from orbital tissues and peripheral blood of patients with GO (1,2). Previous investigations reported that T cell-mediated immune reactions by Th1 cells might predominate in the orbit in early GO, whereas humoral immunity and Th2 cells may play a greater role in the later stages of the disease (3).…”

Section: Introductionmentioning

confidence: 99%

CD4+ T cells and the Th1/Th2 imbalance are implicated in the pathogenesis of Graves' ophthalmopathy

Xia

Zhou²,

Liang³

et al. 2006

Int J Mol Med

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Abstract. Graves' ophthalmopathy (GO) is considered to be an organ-specific autoimmune disease. However, the pathogenesis of GO is incompletely understood at the present time.To clarify the immunological differences between newly diagnosed GO and Graves' disease (GD) without ophthalmopathy or healthy controls (HC), we examined T-cell profile and the Th1/Th2 profile cell balance in GO (n=20), GD (n=20) and HC (n=20) using flow cytometry. We also assessed the influence of methimazole on the immunocyte profiles in patients with GO and GD and analyzed the relationship of the immunologic changes with CAS, FT3, FT4, TRAb, TMA and TGA among the three investigated groups. We report in this study that: 1) The percentage of CD4 + T cells and the ratio of CD4 + /CD8 + cells were higher, but the population of CD8 + T cells was lower in both GO and GD than those of HC (P<0.05); 2) The percentage of CD8 -/IFNÁ + T cells (Th1) and the ratio of CD8 -/IFNÁ + to CD8 -/IL-4 + T cells (Th1/Th2) in GO were considerably higher as compared to those in GD and HC (P<0.05). On the contrary, the population of Th1 cells, as well as the ratio of Th1/Th2 cells, was lower in GD than that of GO and HC (P<0.05); 3) There were no significant differences in T-cell profile and the Th1/Th2 cell balance in either GO or GD patients before and after methimazole treatment; 4) There was a positive correlation of Th1 cell percentage and the Th1/Th2 cell ratio with the clinical activity score (CAS) in GO (P<0.05), whereas CAS in GO had no correlation with the T-cell profile, the percentage of Th2 cells, and TRAb (P>0.05); 5) T-cell subset and the ratio of Th1/Th2 cells did not correlate significantly with FT3, FT4, TRAb, TMA, or TGA in GO and GD (P>0.05). Finally, 6) there were no statistical differences in TRAb, TMA, and TGA between early GO and GD without ophthalmopathy (P>0.05). Collectively, these results indicate that the balance of Th1/Th2 in GO shifts to Th1 dominance and that the cellular immune responses mediated by the Th1-type CD4 + cells might play a dominant role in the pathogenesis of GO, and thus suggest that the Th1 cell percentage and the ratio of Th1/Th2 cell subsets may be potentially utilized as clinical parameters for disease activity, for monitoring the effectiveness of immunosuppressive treatment, or for developing immunospecific forms of therapy for Graves' ophthalmopathy.

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“…Orbital inflammation in early GO is dominated by a T-helper 1 (Th1) cytokine environment with abundant production of cytokines such as IL-1β, IL-2, IFN-γ and TNF-α while in late GO a Th2 dominated cytokine environment with increased production of IL-4, IL-5 and IL-10 might be more prominent [2,27,28,29]. Of these it has been shown that IL-1β stimulates orbital fibroblasts to produce IL-6, IL-8, CCL2, CCL5 and IL-16, which are chemoattractants for B-lymphocytes, neutrophils, monocytes and T-lymphocytes [30,31].…”

Section: The Pathophysiology Of Gomentioning

confidence: 99%

Platelet-Derived Growth Factor: A Key Factor in the Pathogenesis of Graves' Ophthalmopathy and Potential Target for Treatment

Virakul¹,

Steensel²,

Dalm³

et al. 2014

Eur Thyroid J

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Activation of orbital fibroblasts resulting in excessive proliferation, cytokine and hyaluronan production and differentiation into adipocytes, is a main determinant of orbital tissue inflammation and tissue expansion in Graves' ophthalmopathy (GO). During the last years we have shown that the platelet-derived growth factor (PDGF) isoforms PDGF-AA, PDGF-AB and PDGF-BB are increased in orbital tissue from GO patients with active and inactive disease. These PDGF isoforms exhibit the capacity to stimulate proliferation, hyaluronan and cytokine/chemokine production by orbital fibroblasts. Moreover, PDGF-AB and PDGF-BB increase thyroid stimulating hormone receptor (TSHR) expression by orbital fibroblasts, which enhances the orbital fibroblast activating capacity of the THSR stimulatory autoantibodies present in Graves' disease (GD) patients. Of these PDGF isoforms PDGF-BB exhibits the strongest orbital fibroblast activating effects, which is likely related to its ability to bind both the PDGF-receptor (PDGF-R)α and PDGF-Rβ chains. Thus the PDGF-system fulfills important roles in orbital fibroblast activation in both active and inactive GO, which supports a therapeutic rationale for blocking PDGF signaling in GO. Tyrosine kinase inhibitors (TKIs) may be candidates to target PDGF signaling. Of several TKIs tested dasatinib exhibited the highest potency to block PDGF-R signaling in orbital fibroblasts and may represent a promising compound for the treatment of GO as it was effective at low dosage and is associated with less side effects compared to imatinib mesylate and nilotinib. In this review the contribution of PDGF to the pathophysiology of GO as well as therapeutic approaches to target this PDGF-system will be addressed.

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Analysis of orbital T cells in thyroid-associated ophthalmopathy

Cited by 78 publications

References 43 publications

Increased percentage of L-selectin+ and ICAM-1+ peripheral blood CD4+/CD8+ T cells in active Graves' ophthalmopathy.

Increased percentage of L-selectin+ and ICAM-1+ peripheral blood CD4+/CD8+ T cells in active Graves' ophthalmopathy.

CD4+ T cells and the Th1/Th2 imbalance are implicated in the pathogenesis of Graves' ophthalmopathy

Platelet-Derived Growth Factor: A Key Factor in the Pathogenesis of Graves' Ophthalmopathy and Potential Target for Treatment

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