Cytokine profiles of in vivo activated thyroid-infiltrating T cells cloned in the presence or absence of interleukin 4.
We compared Th1 and Th2 cytokines secreted by randomly selected, intrathyroidal CD4+ T cell clones isolated from a patient with Graves' disease using IL-4 + IL-2 versus IL-2 alone. Prior to T cell isolation, PCR of cDNA from the intact thyroid tissue generated IL-4 and IL-10, but not IFN-gamma, products. As controls, IL-4, IFN-gamma and IL-10 cDNA was amplified from stimulated, but not unstimulated, PBMC. All 21 of the nine IL-2 clones and twelve IL-2 + IL-4 clones isolated from the thyroid tissue were CD4+. With the exception of one clone in the IL-2 group, all clones produced IL-10 on stimulation with anti-CD3 and phorbol-12-myristate 13-acetate (PMA) with similar mean values for both groups. The majority of clones in both groups also produced IFN-gamma and IL-4 after stimulation. However, the IL-4:IFN-gamma ratios were significantly higher in clones isolated using IL-2 + IL-4 than in those isolated with IL-2 alone. Furthermore, the distribution of Th1, Th0 and Th2 type clones, defined by their IL-4:IFN-gamma ratios, was also significantly different between those isolated using IL-2 alone and those isolated using IL-2 + IL-4. Of note, although Th0 clones predominated in both groups, Th1 clones were only obtained using IL-2 alone and Th2 clones were only obtained with IL-2 + IL-4. In conclusion, the presence of IL-4 together with IL-2 induces a shift away from a Th1-towards a Th2-response in T cells cloned from in vivo-activated thyroid-infiltrating lymphocytes. This difference in cytokine profile emphasizes that IL-4 is required for cloning T cells representative of a response involving both Th1 and Th2 cells, as occurs in autoimmune thyroid disease.
Guo
J
J
Thyroid Molecular Biology Unit, Veterans' Administration Medical Center and the University of California, San Francisco 94121, USA.
Rapoport
B
B
McLachlan
S M
SM
D000328:Adult; D002850:Chromatography, Gel; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006111:Graves Disease / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D013961:Thyroid Gland / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D013965:Thyroidectomy; D014158:Transcription, Genetic
D016207:Cytokines; D007376:Interleukin-2; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma