In vivo mechanisms of acquired thymic tolerance.

Abstract:

:Injection of antigen into the thymus of adult animals induces specific systemic tolerance, but the mechanisms of acquired thymic tolerance are not well understood. To investigate these mechanisms we used a model of intrathymic injection of ovalbumin (OVA) in BALB/c mice. We show an antigen-specific decrease in proliferative responses to OVA, as well as a significant decrease in antigen-specific IL-2 secretion and IFN-gamma production by splenocytes and lymph node cells of tolerant mice. Addition of recombinant IL-2 in vitro reversed the defect in IFN-gamma production by cells from OVA-tolerized animals, but did not reverse the proliferation or IL-2 production defects. By using an adoptive transfer system, where a small population of OVA peptide-specific CD4+ TCR transgenic T cells are transferred into syngeneic normal recipients, we show an absence of peripheral antigen-dependent clonal expansion of transferred CD4+ TCR transgenic cells in tolerant mice in vivo. There was an increase in clonotype-positive T cells in the thymus after immunization, confirming that activated T cells circulate through the thymus. Furthermore, thymectomy after intrathymic injection abrogates the effect of acquired thymic tolerance and restores antigen-dependent clonal expansion in vivo. We conclude that intrathymic injection of antigen induces Th1 cell unresponsiveness and prevents the peripheral expansion of antigen-specific CD4(+) T cells in vivo. This is the first demonstration that in acquired thymic tolerance antigen-specific T cells circulate to the thymus where they may be anergized or ultimately deleted.

journal_name

Cell Immunol

journal_title

Cellular immunology

authors

Chen W,Issazadeh S,Sayegh MH,Khoury SJ

doi

10.1006/cimm.1997.1165

subject

Has Abstract

pub_date

1997-08-01 00:00:00

pages

165-73

issue

2

eissn

0008-8749

issn

1090-2163

pii

S0008-8749(97)91165-5

journal_volume

179

pub_type

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