T-cell activation and receptor downmodulation precede deletion induced by mucosally administered antigen.
The fate of antigen-specific T cells was characterized in myelin basic protein (MBP) T-cell receptor (TCR) transgenic (Tg) mice after oral administration of MBP. Peripheral Th cells are immediately activated in vivo, as indicated by upregulation of CD69 and increased cytokine responses (Th1 and Th2). Concurrently, surface TCR expression diminishes and internal TCR levels increase. When challenged for experimental autoimmune encephalomyelitis during TCR downmodulation, Tg mice are protected from disease. To characterize Th cells at later times after antigen feeding, it was necessary to prevent thymic release of naive Tg cells. Therefore, adult Tg mice were thymectomized before treatment. TCR expression returns in thymectomized Tg mice 3 days after MBP feeding and then ultimately declines in conjunction with MBP-specific proliferation and cytokine responses (Th1-type and Th2-type). The decline correlates with an increase in apoptosis. Collectively, these results demonstrate that a high dose of fed antigen induces early T-cell activation and TCR downmodulation, followed by an intermediate stage of anergy and subsequent deletion.
Benson
J M
JM
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, College of Medicine and Public Health, Columbus, Ohio 43210-1239, USA.
Campbell
K A
KA
Guan
Z
Z
Gienapp
I E
IE
Stuckman
S S
SS
Forsthuber
T
T
Whitacre
C C
CC
D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis; D017637:Clonal Deletion; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis* / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013934:Thymectomy
D016207:Cytokines; D004676:Myelin Basic Protein; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta