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

Baptista AP, Roozendaal R, Reijmers RM, Koning JJ, Unger WW, Greuter M, Keuning ED, Molenaar R, Goverse G, Sneeboer MM, den Haan JM, Boes M, Mebius RE - Elife (2014)

Bottom Line: In this study, we show that MHC-II expression on lymph node stromal cells is additionally required for homeostatic maintenance of regulatory T cells (Tregs) and maintenance of immune quiescence.MHC-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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, Amsterdam, Netherlands.

ABSTRACT
Non-hematopoietic lymph node stromal cells shape immunity by inducing MHC-I-dependent deletion of self-reactive CD8(+) T cells and MHC-II-dependent anergy of CD4(+) T cells. In this study, we show that MHC-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 MHC-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. MHC-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.

No MeSH data available.


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Mentions: We agree with this reviewer that analysis of MHC-II expression in transplanted lymph nodes is critical. We have now included such analysis in Figure 2–figure supplement 1. We show that whereas dendritic cells and ETAC-like cells remain MHC-II positive, lymph node stromal cells exhibit a significant decrease in MHC-II expression in MHC-II-/- transplants as compared to wild-type transplants. As the reviewer points out, the MHC-II expression detected in MHC-II-/- transplanted stromal cells is likely to have been acquired from dendritic cells (Dubrot et al. JEM 2014). The analysis suggested by the reviewer to address this point, unfortunately, could not be performed, as transfer of MHC-II-/- bone marrow into wild-type recipients leads to severe disease and death of the chimeric animals (Marguerat et al, JImmunol 1999). Finally, as shown in the revised Figure 3–figure supplement 1, no difference in Treg proliferation in the endogenous lymph nodes of wild-type and MHC-II-/- transplant recipients was observed. Thus, direct comparison of Treg proliferation between MHC-II-/- transplants and the endogenous lymph nodes of MHC-II-/-transplant recipients, showed a significant reduction in Treg proliferation in the former (see Author response image 2). Together, these data suggest that Treg proliferation was specifically impaired in MHC-II-/- transplants.Author response image 2.


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

Baptista AP, Roozendaal R, Reijmers RM, Koning JJ, Unger WW, Greuter M, Keuning ED, Molenaar R, Goverse G, Sneeboer MM, den Haan JM, Boes M, Mebius RE - Elife (2014)

© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4270074&req=5

Mentions: We agree with this reviewer that analysis of MHC-II expression in transplanted lymph nodes is critical. We have now included such analysis in Figure 2–figure supplement 1. We show that whereas dendritic cells and ETAC-like cells remain MHC-II positive, lymph node stromal cells exhibit a significant decrease in MHC-II expression in MHC-II-/- transplants as compared to wild-type transplants. As the reviewer points out, the MHC-II expression detected in MHC-II-/- transplanted stromal cells is likely to have been acquired from dendritic cells (Dubrot et al. JEM 2014). The analysis suggested by the reviewer to address this point, unfortunately, could not be performed, as transfer of MHC-II-/- bone marrow into wild-type recipients leads to severe disease and death of the chimeric animals (Marguerat et al, JImmunol 1999). Finally, as shown in the revised Figure 3–figure supplement 1, no difference in Treg proliferation in the endogenous lymph nodes of wild-type and MHC-II-/- transplant recipients was observed. Thus, direct comparison of Treg proliferation between MHC-II-/- transplants and the endogenous lymph nodes of MHC-II-/-transplant recipients, showed a significant reduction in Treg proliferation in the former (see Author response image 2). Together, these data suggest that Treg proliferation was specifically impaired in MHC-II-/- transplants.Author response image 2.

Bottom Line: In this study, we show that MHC-II expression on lymph node stromal cells is additionally required for homeostatic maintenance of regulatory T cells (Tregs) and maintenance of immune quiescence.MHC-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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, Amsterdam, Netherlands.

ABSTRACT
Non-hematopoietic lymph node stromal cells shape immunity by inducing MHC-I-dependent deletion of self-reactive CD8(+) T cells and MHC-II-dependent anergy of CD4(+) T cells. In this study, we show that MHC-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 MHC-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. MHC-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.

No MeSH data available.


Related in: MedlinePlus