ANALYSIS OF T-CELL ANTIGEN RECEPTOR VARIABLE REGION GENE USAGE IN PATIENTS WITH THYROID-RELATED PRETIBIAL DERMOPATHY

It is unknown whether T cells infiltrating the pretibial skin of patie nts with thyroid-related pretibial dermopathy represent a primary immu ne response or participate in a nonspecific inflammatory process, To c haracterize these T cells at the molecular level, we examined the T-ce ll antigen receptor variable region gene usage in pretibial skin biops y specimens obtained from patients with early and late stages of preti bial dermopathy and from individuals with unrelated inflammatory condi tions of the pretibial skin, RNA extracted from pretibial biopsy speci mens and peripheral blood lymphocytes was reverse transcribed and ampl ified with the polymerase chain reaction and 22 V alpha and 23 V beta gene-specific oligonucleotide primers, The resulting T-cell receptor ( TcR) V alpha and V beta transcripts were verified by Southern hybridiz ation analysis using TcR C-region-specific, digoxigenin-labeled oligon ucleotide probes. Compared with matched peripheral blood lymphocytes, the pretibial TcR V alpha and V beta gene repertoire expressed was het erogeneous but revealed marked restriction of V alpha and V beta gene usage in samples derived from patients with active inflammatory pretib ial dermopathy of recent onset, In contrast, greater diversity of the TcR V alpha gene repertoire and loss of TcR V beta gene restriction we re noted in patients with longstanding, clinically inactive pretibial dermopathy. TcR V gene usage in pretibial tissue and peripheral blood lymphocyte samples obtained from control subjects was unrestricted, Li mited variability of TcR V gene usage in early pretibial dermopathy ma y reflect a primary immune response of antigen-specific T lymphocytes infiltrating the pretibial skin in thyroid-related pretibial dermopath y.