title: Selection of human TcR V gene families in autologous mixed lymphocyte reactions: relevance to autoimmune immunopathology.
abstract: We have postulated that in vivo autologous mixed lymphocyte reactions (AMLRs) are one mechanism in the development of the intrathyroidal lymphocytic infiltration of human autoimmune thyroid disease. Such a mechanism would explain the significant numbers of self-reactive T cells present in thyroid infiltrates as evidenced by cloning studies. However, infiltrating T cells in a variety of autoimmune disease including autoimmune thyroid disease, demonstrate bias in their use of T cell receptor (TcR) V gene families. In order to examine whether such TcR V gene bias may occur secondary to non-antigen specific in vivo AMLRs rather than secondary to specific autoantigen driven mechanisms we have examined the human TcR repertoire after prolonged AMLRs in vitro. Using 5 healthy donors in 1, 2 and 3 weeks AMLRs we showed stimulation indices of 3.1-6.5 after 3 weeks. The hTcR V alpha and V beta gene repertoire was assessed using the PCR technique and revealed an almost complete repertoire of V gene families at the beginning of the studies while at the end of 3 weeks a mean of only 5.2 V alpha genes were transcribed. Less restriction was seen in the hTcR V beta repertoire with a mean of 9 V beta genes used. These data demonstrate that the AMLR is able to mimic the marked bias in hTcR V gene family use seen within the inflammatory infiltrates of autoimmune diseases.
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
authors.forename: N
authors.initials: N
authors.lastname: Lahat
authors.forename: A
authors.initials: A
authors.lastname: Ben-Nun
authors.forename: A
authors.initials: A
authors.lastname: Kinarty
authors.forename: T F
authors.initials: TF
authors.lastname: Davies
mesh_terms: D000328:Adult; D015551:Autoimmunity / Q000235:genetics* / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D007959:Lymphocyte Culture Test, Mixed; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D017634:Self Tolerance / Q000235:genetics / Q000276:immunology; D013997:Time Factors
chemical_list: D011948:Receptors, Antigen, T-Cell