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Published on: July 22, 2011
Type-1 response in peripheral CD4+ and CD8+ T cells from patients with Hashimoto's thyroiditis
Gherardo Mazziotti1, Francesca Sorvillo, Caterina Naclerio
1F. Magrassi & A. Lanzara Department of Clinical and Experimental Medicine, Second University of Naples, via Crispi 44, 80121 Naples, Italy.
Insights
Hashimoto's thyroiditis (HT) patients exhibit increased type-1 immune responses in CD4+ and CD8+ T lymphocytes, particularly when hypothyroidism is present. This immune activation is linked to thyroid function, suggesting lymphocytes may indicate thyroid immune involvement.
Area of Science:
- Immunology
- Endocrinology
- Cell Biology
Background:
- Hashimoto's thyroiditis (HT) is an autoimmune disease affecting the thyroid gland.
- The role of peripheral T lymphocytes in HT pathogenesis requires further elucidation.
- Understanding T-cell responses, specifically cytokine production, is crucial for comprehending HT.
Purpose of the Study:
- To analyze intracellular cytokine expression in peripheral CD4+ and CD8+ lymphocytes in HT patients.
- To investigate the type-1 immune response in these lymphocyte subpopulations.
- To correlate cytokine expression with thyroid function status (euthyroid vs. hypothyroid).
Main Methods:
- Single-cell analysis of intracellular cytokine expression (interferon-gamma [IFN-gamma] and IL-4).
- Assay performed on peripheral CD4+ and CD8+ lymphocytes from 29 HT patients and 20 healthy controls.
- Lymphocytes were stimulated with phorbolmyristate acetate (PMA).
Main Results:
- HT patients showed higher CD4+ IFN-gamma+, CD4+ IL-4+, and CD8+ IFN-gamma+ cells compared to controls.
- Euthyroid HT patients had increased CD4+ IL-4+ expression.
- Hypothyroid HT patients exhibited elevated IFN-gamma expression in both CD4+ and CD8+ lymphocytes, with lower CD4+ IL-4+ expression compared to euthyroid patients.
Conclusions:
- Peripheral CD4+ and CD8+ T lymphocytes in HT patients demonstrate a type-1 activation.
- This type-1 activation is strongly correlated with the presence of hypothyroidism.
- Peripheral lymphocytes may serve as a marker for thyroid immune involvement in HT.
Objective:
In this study we performed single-cell analysis of the intracellular cytokine expression in peripheral CD4+ and CD8+ lymphocytes from patients with Hashimoto's thyroiditis (HT) to investigate the type-1 response separately for the two lymphocyte sub-populations.
Design And Methods:
Twenty-nine patients affected by HT and 20 healthy subjects, matched for sex and age, were enrolled. After the analysis of the lymphocyte sub-populations, the intracellular content of interferon-gamma (IFN-gamma) in phorbolmyristate acetate (PMA)-stimulated CD4+ and CD8+ lymphocytes was assayed. Moreover, the CD4+ lymphocytes were also evaluated for the intracellular expression of IL-4.
Results:
No significant differences in CD3+, CD4+ and CD8+ lymphocytes were found between HT patients and control subjects. However, the HT patients showed higher numbers of CD4+ IFN-gamma+, CD4+ IL-4+ and CD8+ IFN-gamma+ (t-test, P< or =0.001) cells than the control subjects. Analysing the intracellular expression of IFN-gamma and IL-4 in relation to thyroid function, we found that the euthyroid patients (18 cases) showed more expression of IL-4 in CD4+ lymphocytes than the control subjects, without any significant modification of IFN-gamma expression in CD4+ and CD8+ lymphocytes. However, the hypothyroid patients (11 cases) showed an increase of IFN-gamma expression in both CD4+ and CD8+ lymphocytes with respect to the control subjects and the euthyroid patients. Moreover, the expression of IL-4 in CD4+ cells from hypothyroid patients was significantly lower than that seen in the euthyroid cases and comparable to that found in the control subjects.
Conclusions:
Our study has demonstrated that the peripheral CD4+ and CD8+ T lymphocytes from the HT patients show a type-1 activation strictly correlated to the occurrence of hypothyroidism. Further studies will be needed to clarify the exact role of peripheral lymphocytes in HT and whether they could provide a reliable marker of thyroid immune involvement.
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