Molecular heterogeneity of a Graves' thyroid-infiltrating T cell population rich in CD8+ and gamma delta+ T cells.

Abstract

We report here on the isolation and repertoire characterization of a Graves' thyroid T cell population which, unlike most Graves' thyroid T cell isolates reported before, was rich in CD4-CD8- T cells (16%, all TcR gamma delta+) and CD8+ T cells (75%) [TcR alpha beta+ (59%) and TcR gamma delta+ (16%)]. Only 7% of the isolated T cells were CD4+. By contrast, < 2% of peripheral blood mononuclear cells from the same patient were gamma delta+ and < 14% were CD8+. Sequence analysis of 18 TcR delta cDNAs prepared from these cells indicated the presence of at least 17 different gamma delta+ T cell clonotypes with molecularly heterogeneous antigen-binding site sequences. As opposed to most peripheral blood gamma delta+ T cells (express V delta 2 TcRs), 13 of the 17 different TcR delta clonotypes used a V delta 1 gene, although PCR amplification of TcR gamma- and TcR delta-specific cDNAs with V delta- and V gamma-gene family-specific oligonucleotides confirmed usage of all 4 V gamma and all 6 V delta families. Sequence analysis of 21 TcR alpha cDNAs from a TcR alpha-specific cDNA library indicated the presence of at least 12 different clonotypes, using 8 different V alpha gene families and heterogeneous antigen-binding site sequences. These results are in contrast with the selective V alpha gene usage reported for other intrathyroidal T cell subpopulations in autoimmune thyroid disease.