Class II HLA-DR antigens on non-autoimmune human thyroid cells stimulate autologous T cells with high suppressor activity.
Human autoimmune thyroid cells "spontaneously" express MHC-class II antigens. These antigens have been assumed to trigger thyroid-specific helper T cell clones, leading in turn to the expansion of thyroid autoantibody-secreting B cells. Thyroid cells derived from non-autoimmune subjects do not express MHC-class antigens, but these can be readily induced with gamma-interferon. We have addressed the issue of whether it is sufficient for normal thyroid cells to bear class II antigens in order to trigger autologous T cells. We found that non-autoimmune thyrocytes expressing DR antigens fail to stimulate autologous resting T cells. However, proliferative activity and interleukin-2 secretion were observed when fresh T cells were first triggered by autologous non-T cells and then incubated with thyrocytes. More CD8 than CD4 cells proliferated in the T:thyrocyte cultures, but CD4 cells were necessary for the proliferation and interleukin-2 secretion. Addition of antibodies to thyroglobulin or to DR antigens inhibited T cell proliferation and interleukin-2 secretion, thus pointing to T cell recognition of both thyroid-specific and DR antigens. Evaluation of the function of the thyroid stimulated T cells revealed very potent suppressor but negligible helper and cytotoxic activities. It would seem, therefore, that DR-restricted T cell activation by autologous antigen on non-autoimmune thyroid cells does occur, but since it results in enhanced suppression, its nature seems protective, thus leading to maintenance of immunological self-tolerance.
Lahat
N
N
Immunology Research Unit, Carmel Hospital, Haifa, Israel.
Sheinfeld
M
M
Sobel
E
E
Baron
E
E
Kraiem
Z
Z
D000938:Antigen-Presenting Cells; D002455:Cell Division; D002478:Cells, Cultured / Q000187:drug effects; D006684:HLA-DR Antigens / Q000032:analysis / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000032:analysis / Q000378:metabolism*; D008213:Lymphocyte Activation; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013961:Thyroid Gland / Q000187:drug effects / Q000276:immunology*
D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D007371:Interferon-gamma