Lymph node stromal cells constrain immunity via MHC class II self-antigen presentation

A. P. Baptista; R. Roozendaal; R. M. Reijmers; J. J. Koning; W. W. Unger; M. Greuter; E. D. Keuning; R. Molenaar; G. Goverse; M. M. S. Sneeboer; J. M. M. den Haan; M. Boes; R. E. Mebius

doi:10.7554/eLife.04433

Lymph node stromal cells constrain immunity via MHC class II self-antigen presentation

A. P. Baptista^*, R. Roozendaal, R. M. Reijmers, J. J. Koning, W. W. Unger, M. Greuter, E. D. Keuning, R. Molenaar, G. Goverse, M. M. S. Sneeboer, J. M. M. den Haan, M. Boes, R. E. Mebius

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Non-hematopoietic lymph node stromal cells shape immunity by inducing WIC-I-dependent deletion of self-reactive CD8(+) T cells and WIC-II-dependent anergy of CD4(+) T cells. Here, we show that WIC-II expression on lymph node stromal cells is additionally required for homeostatic maintenance of regulatory T cells (Tregs) and maintenance of immune quiescence. In the absence of WIC-II expression in lymph node transplants, i.e. on lymph node stromal cells, CD4(+) as well as CD8(+) T cells became activated, ultimately resulting in transplant rejection. WIC-II self-antigen presentation by lymph node stromal cells allowed the non-proliferative maintenance of antigen-specific Tregs and constrained antigen-specific immunity. Altogether, our results reveal a novel mechanism by which lymph node stromal cells regulate peripheral immunity.

Original language	English
Number of pages	47
Journal	eLife
Volume	3
DOIs	https://doi.org/10.7554/eLife.04433
Publication status	Published - 19 Nov 2014

Keywords

FIBROBLASTIC RETICULAR CELLS
AIRE-EXPRESSING CELLS
REGULATORY T-CELLS
DENDRITIC CELLS
PERIPHERAL TOLERANCE
HOMEOSTASIS
POPULATION
SYSTEM
GENES
MICE

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10.7554/eLife.04433

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@article{f66af8f8e05542499052bf9e321ec5fb,

title = "Lymph node stromal cells constrain immunity via MHC class II self-antigen presentation",

abstract = "Non-hematopoietic lymph node stromal cells shape immunity by inducing WIC-I-dependent deletion of self-reactive CD8(+) T cells and WIC-II-dependent anergy of CD4(+) T cells. Here, we show that WIC-II expression on lymph node stromal cells is additionally required for homeostatic maintenance of regulatory T cells (Tregs) and maintenance of immune quiescence. In the absence of WIC-II expression in lymph node transplants, i.e. on lymph node stromal cells, CD4(+) as well as CD8(+) T cells became activated, ultimately resulting in transplant rejection. WIC-II self-antigen presentation by lymph node stromal cells allowed the non-proliferative maintenance of antigen-specific Tregs and constrained antigen-specific immunity. Altogether, our results reveal a novel mechanism by which lymph node stromal cells regulate peripheral immunity.",

keywords = "FIBROBLASTIC RETICULAR CELLS, AIRE-EXPRESSING CELLS, REGULATORY T-CELLS, DENDRITIC CELLS, PERIPHERAL TOLERANCE, HOMEOSTASIS, POPULATION, SYSTEM, GENES, MICE",

author = "Baptista, {A. P.} and R. Roozendaal and Reijmers, {R. M.} and Koning, {J. J.} and Unger, {W. W.} and M. Greuter and Keuning, {E. D.} and R. Molenaar and G. Goverse and Sneeboer, {M. M. S.} and {den Haan}, {J. M. M.} and M. Boes and Mebius, {R. E.}",

year = "2014",

month = nov,

day = "19",

doi = "10.7554/eLife.04433",

language = "English",

volume = "3",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications",

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TY - JOUR

T1 - Lymph node stromal cells constrain immunity via MHC class II self-antigen presentation

AU - Baptista, A. P.

AU - Roozendaal, R.

AU - Reijmers, R. M.

AU - Koning, J. J.

AU - Unger, W. W.

AU - Greuter, M.

AU - Keuning, E. D.

AU - Molenaar, R.

AU - Goverse, G.

AU - Sneeboer, M. M. S.

AU - den Haan, J. M. M.

AU - Boes, M.

AU - Mebius, R. E.

PY - 2014/11/19

Y1 - 2014/11/19

N2 - Non-hematopoietic lymph node stromal cells shape immunity by inducing WIC-I-dependent deletion of self-reactive CD8(+) T cells and WIC-II-dependent anergy of CD4(+) T cells. Here, we show that WIC-II expression on lymph node stromal cells is additionally required for homeostatic maintenance of regulatory T cells (Tregs) and maintenance of immune quiescence. In the absence of WIC-II expression in lymph node transplants, i.e. on lymph node stromal cells, CD4(+) as well as CD8(+) T cells became activated, ultimately resulting in transplant rejection. WIC-II self-antigen presentation by lymph node stromal cells allowed the non-proliferative maintenance of antigen-specific Tregs and constrained antigen-specific immunity. Altogether, our results reveal a novel mechanism by which lymph node stromal cells regulate peripheral immunity.

AB - Non-hematopoietic lymph node stromal cells shape immunity by inducing WIC-I-dependent deletion of self-reactive CD8(+) T cells and WIC-II-dependent anergy of CD4(+) T cells. Here, we show that WIC-II expression on lymph node stromal cells is additionally required for homeostatic maintenance of regulatory T cells (Tregs) and maintenance of immune quiescence. In the absence of WIC-II expression in lymph node transplants, i.e. on lymph node stromal cells, CD4(+) as well as CD8(+) T cells became activated, ultimately resulting in transplant rejection. WIC-II self-antigen presentation by lymph node stromal cells allowed the non-proliferative maintenance of antigen-specific Tregs and constrained antigen-specific immunity. Altogether, our results reveal a novel mechanism by which lymph node stromal cells regulate peripheral immunity.

KW - FIBROBLASTIC RETICULAR CELLS

KW - AIRE-EXPRESSING CELLS

KW - REGULATORY T-CELLS

KW - DENDRITIC CELLS

KW - PERIPHERAL TOLERANCE

KW - HOMEOSTASIS

KW - POPULATION

KW - SYSTEM

KW - GENES

KW - MICE

U2 - 10.7554/eLife.04433

DO - 10.7554/eLife.04433

M3 - Article

C2 - 25407678

SN - 2050-084X

VL - 3

JO - eLife

JF - eLife

ER -

Lymph node stromal cells constrain immunity via MHC class II self-antigen presentation

Abstract

Keywords

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