Lymph node stromal cells negatively regulate antigen-specific CD4+ T cell responses

Abe, Jun; Shichino, Shigeyuki; Ueha, Satoshi; Hashimoto, Shin-ichi; Tomura, Michio; Inagaki, Yutaka; Stein, Jens Volker; Matsushima, Kouji (2014). Lymph node stromal cells negatively regulate antigen-specific CD4+ T cell responses. Journal of immunology, 193(4), pp. 1636-1644. American Association of Immunologists 10.4049/jimmunol.1302946

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Lymph node (LN) stromal cells (LNSCs) form the functional structure of LNs and play an important role in lymphocyte survival and the maintenance of immune tolerance. Despite their broad spectrum of function, little is known about LNSC responses during microbial infection. In this study, we demonstrate that LNSC subsets display distinct kinetics following vaccinia virus infection. In particular, compared with the expansion of other LNSC subsets and the total LN cell population, the expansion of fibroblastic reticular cells (FRCs) was delayed and sustained by noncirculating progenitor cells. Notably, newly generated FRCs were preferentially located in perivascular areas. Viral clearance in reactive LNs preceded the onset of FRC expansion, raising the possibility that viral infection in LNs may have a negative impact on the differentiation of FRCs. We also found that MHC class II expression was upregulated in all LNSC subsets until day 10 postinfection. Genetic ablation of radioresistant stromal cell-mediated Ag presentation resulted in slower contraction of Ag-specific CD4(+) T cells. We propose that activated LNSCs acquire enhanced Ag-presentation capacity, serving as an extrinsic brake system for CD4(+) T cell responses. Disrupted function and homeostasis of LNSCs may contribute to immune deregulation in the context of chronic viral infection, autoimmunity, and graft-versus-host disease.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Abe, Jun and Stein, Jens Volker

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0022-1767

Publisher:

American Association of Immunologists

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

07 Apr 2015 13:16

Last Modified:

07 Apr 2015 13:16

Publisher DOI:

10.4049/jimmunol.1302946

PubMed ID:

25024385

BORIS DOI:

10.7892/boris.66365

URI:

https://boris.unibe.ch/id/eprint/66365

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