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PMID: 3484777 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Intrathymic presentation of circulating non-MHC antigens by medullary dendritic cells. An antigen-dependent microenvironment for T cell differentiation.

The Journal of experimental medicine ·Vol. 163 ·No. 2 ·1986-02-01 ·Pages 231-46

Kyewski BA, Fathman CG, Rouse RV

Abstract

We present evidence for intrathymic presentation of soluble circulating antigens in vivo. Our results show that proteins of different molecular weight enter the mouse thymus rapidly after i.v. injection. The intrathymic presence of antigen was assayed by proliferation of cloned antigen-specific T helper cells, which were cocultured with purified thymic stromal cells; stromal cells were isolated and purified as lymphostromal cell complexes, which preexist in vivo. Antigen presentation copurified with non-adherent medullary dendritic cells (DC) (interdigitating cells). I-A- cortical macrophages forming thymocyte rosettes in vivo and I-A+ cortical epithelial cells forming thymic nurse cells (TNC) in vivo did not act as antigen presenting cells (APC) after antigen pulsing in vivo or in vitro. Thymic APC turn over physiologically and are rapidly replaced (within 2-5 wk) after lethal irradiation by donor bone marrow-derived cells. The frequency of thymocyte-DC interactions in vivo strictly correlates with thymic T cell differentiation, and is independent of the immune status of the animal. Fetal thymic APC seem to be secluded from antigen in the maternal circulation. Thymic DC-ROS probably represent the microenvironment where maturing T cells first encounter non-MHC antigens in the context of self-MHC antigens.

MeSH Terms
Animals Antigen-Presenting Cells/physiology Cell Differentiation Female Histocompatibility Antigens Class II/immunology Immune Tolerance Mice Mice, Inbred BALB C Mice, Inbred C3H Mice, Inbred C57BL Rosette Formation Spleen/cytology,immunology T-Lymphocytes/cytology,immunology Thymus Gland/cytology,growth & development,immunology
Chemicals
Histocompatibility Antigens Class II
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kyewski B A
Fathman C G
Rouse R V
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46 references, click to expand
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.163.2.231
Published
1986-02-01
Pages
231-46
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2188029
Subset
IM
Grants
NIAID NIH HHS · AI 18635 · United States
NIAID NIH HHS · AI 18705 · United States
External Links
PubMed source DOI: 10.1084/jem.163.2.231 PMC Full Text View journal details
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