Evidence for selective accumulation of intrathyroidal T lymphocytes in human autoimmune thyroid disease based on T cell receptor V gene usage.
We have investigated the T cell receptor V alpha and V beta gene family usage by T lymphocytes infiltrating affected thyroids in patients with autoimmune thyroid disease. We show that the intrathyroidal T lymphocytes from patients (n = 6) with autoimmune thyroid disease display a widespread usage of V beta gene families with an average of 14.4/19 V beta gene families similar to the peripheral T lymphocytes of the same patients. Because we recently reported that the utilization of V alpha gene families is markedly reduced within these mitogen-stimulated intrathyroidal T cell populations, as well as within intact tissue from similar patients (n = 4) (overall mean of 4.0/18 families detected), these results indicate that in thyroids of patients with autoimmune thyroid disease the lymphocytes are selectively accumulating based on their V alpha rather than V beta elements. This preferential hTcR V alpha and widespread V beta gene usage was not mimicked in most 7-d autologous mixed lymphocyte reactions using non-T cell stimulators (n = 6) or EB-virus immortalized autologous B cell lines (n = 3). Hence, the selective V gene utilization by intrathyroidal T cells is likely to be secondary to multiepitopic thyroidal autoantigens activating thyroid infiltrating T cells or to the presence of a superantigenlike thyroidal self-antigen, capable of determining a selective infiltration or activation of a variety of T lymphocytes on the basis of their V alpha gene usage.
Davies
T F
TF
Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029.
Martin
A
A
Concepcion
E S
ES
Graves
P
P
Lahat
N
N
Cohen
W L
WL
Ben-Nun
A
A
D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D001483:Base Sequence; D015139:Blotting, Southern; D005784:Gene Amplification; D006111:Graves Disease / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008969:Molecular Sequence Data; D009841:Oligonucleotides; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D012265:Ribonucleotides; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013959:Thyroid Diseases / Q000276:immunology*; D013964:Thyroid Neoplasms / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000276:immunology
D001323:Autoantibodies; D009841:Oligonucleotides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012265:Ribonucleotides