Limited capacity for tolerization of CD4+ T cells specific for a pancreatic beta cell neo-antigen.
Mice transgenic for SV40 T antigen (Tag) under control of the rat insulin promoter (RIP) develop two alternative immunological phenotypes: tolerance or autoimmunity towards Tag. We utilized the T cell receptor (TCR) genes expressed in a Tag-specific CD4+ cell from an autoimmune RIP-Tag mouse to generate two lines of TCR transgenic mice in which either 10% or 90% of peripheral T cells express the transgenic TCR. When cross-bred to the tolerant RIP1-Tag2 line, mice from the low frequency TCR line showed partial deletion of peripheral Tag-specific T cells and nonresponsiveness of those that remained. In contrast, crossbred mice in which transgenic T cells comprised a majority of the T cell population were nontolerant both in vivo and in vitro. Thus, tolerization of CD4+ T cells specific for a rare self-antigen may fail if too many autoreactive T cells develop.
Förster
I
I
Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0534, USA.
Hirose
R
R
Arbeit
J M
JM
Clausen
B E
BE
Hanahan
D
D
D000818:Animals; D000888:Antibodies, Anti-Idiotypic; D000952:Antigens, Polyomavirus Transforming / Q000276:immunology / Q000502:physiology; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003001:Cloning, Molecular; D005434:Flow Cytometry; D006825:Hybridomas; D007108:Immune Tolerance / Q000276:immunology; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000952:Antigens, Polyomavirus Transforming; D011948:Receptors, Antigen, T-Cell