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

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Antonio P Baptista ◽  
Ramon Roozendaal ◽  
Rogier M Reijmers ◽  
Jasper J Koning ◽  
Wendy W Unger ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Cd8 T Cells ◽  
Stromal Cells ◽  
Transplant Rejection ◽  
Mhc Ii ◽  
Self Antigen ◽  
Lymph Node Stromal Cells

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.

scholarly journals Author response: Lymph node stromal cells constrain immunity via MHC class II self-antigen presentation

2014 ◽  
Author(s):  
Antonio P Baptista ◽  
Ramon Roozendaal ◽  
Rogier M Reijmers ◽  
Jasper J Koning ◽  
Wendy W Unger ◽  
...  
Keyword(s):  
Lymph Node ◽  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Stromal Cells ◽  
Class Ii ◽  
Author Response ◽  
Self Antigen ◽  
Lymph Node Stromal Cells

scholarly journals Lymph Node Stromal Cells Generate Antigen-Specific Regulatory T Cells and Control Autoreactive T and B Cell Responses

Cell Reports ◽  
2020 ◽  
Vol 30 (12) ◽  
pp. 4110-4123.e4 ◽  
Author(s):  
Reza Nadafi ◽  
Catarina Gago de Graça ◽  
Eelco D. Keuning ◽  
Jasper J. Koning ◽  
Sander de Kivit ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
Regulatory T Cells ◽  
B Cell ◽  
Stromal Cells ◽  
Cell Responses ◽  
B Cell Responses ◽  
And Control ◽  
Lymph Node Stromal Cells

scholarly journals Human Lymph Node Stromal Cells Have the Machinery to Regulate Peripheral Tolerance during Health and Rheumatoid Arthritis

2020 ◽  
Vol 21 (16) ◽  
pp. 5713
Author(s):  
Janine S. Hähnlein ◽  
Reza Nadafi ◽  
Tineke A. de Jong ◽  
Johanna F. Semmelink ◽  
Ester B. M. Remmerswaal ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Lymph Node ◽  
Antigen Presentation ◽  
Stromal Cells ◽  
Immune Modulation ◽  
Ex Vivo ◽  
Human Leukocyte ◽  
Interferon Γ ◽  
Peripheral Tolerance ◽  
Lymph Node Stromal Cells

Background: In rheumatoid arthritis (RA) the cause for loss of tolerance and anti-citrullinated protein antibody (ACPA) production remains unidentified. Mouse studies showed that lymph node stromal cells (LNSCs) maintain peripheral tolerance through presentation of peripheral tissue antigens (PTAs). We hypothesize that dysregulation of peripheral tolerance mechanisms in human LNSCs might underlie pathogenesis of RA. Method: Lymph node (LN) needle biopsies were obtained from 24 RA patients, 23 individuals positive for RA-associated autoantibodies but without clinical disease (RA-risk individuals), and 14 seronegative healthy individuals. Ex vivo human LNs from non-RA individuals were used to directly analyze stromal cells. Molecules involved in antigen presentation and immune modulation were measured in LNSCs upon interferon γ (IFNγ) stimulation (n = 15). Results: Citrullinated targets of ACPAs were detected in human LN tissue and in cultured LNSCs. Human LNSCs express several PTAs, transcription factors autoimmune regulator (AIRE) and deformed epidermal autoregulatory factor 1 (DEAF1), and molecules involved in citrullination, antigen presentation, and immunomodulation. Overall, no clear differences between donor groups were observed with exception of a slightly lower induction of human leukocyte antigen-DR (HLA-DR) and programmed cell death 1 ligand (PD-L1) molecules in LNSCs from RA patients. Conclusion: Human LNSCs have the machinery to regulate peripheral tolerance making them an attractive target to exploit in tolerance induction and maintenance.

scholarly journals Lymph node stromal cells acquire peptide–MHCII complexes from dendritic cells and induce antigen-specific CD4+ T cell tolerance

2014 ◽  
Vol 211 (6) ◽  
pp. 1153-1166 ◽  
Author(s):  
Juan Dubrot ◽  
Fernanda V. Duraes ◽  
Lambert Potin ◽  
Francesca Capotosti ◽  
Dale Brighouse ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Lymph Node ◽  
T Cell ◽  
Stromal Cells ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Cell Functions ◽  
Mhcii Expression ◽  
Lymph Node Stromal Cells

Dendritic cells (DCs), and more recently lymph node stromal cells (LNSCs), have been described to tolerize self-reactive CD8+ T cells in LNs. Although LNSCs express MHCII, it is unknown whether they can also impact CD4+ T cell functions. We show that the promoter IV (pIV) of class II transactivator (CIITA), the master regulator of MHCII expression, controls endogenous MHCII expression by LNSCs. Unexpectedly, LNSCs also acquire peptide–MHCII complexes from DCs and induce CD4+ T cell dysfunction by presenting transferred complexes to naive CD4+ T cells and preventing their proliferation and survival. Our data reveals a novel, alternative mechanism where LN-resident stromal cells tolerize CD4+ T cells through the presentation of self-antigens via transferred peptide–MHCII complexes of DC origin.

scholarly journals Differential roles of migratory and resident DCs in T cell priming after mucosal or skin HSV-1 infection

2009 ◽  
Vol 206 (2) ◽  
pp. 359-370 ◽  
Author(s):  
Heung Kyu Lee ◽  
Melodie Zamora ◽  
Melissa M. Linehan ◽  
Norifumi Iijima ◽  
David Gonzalez ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
Antigen Presentation ◽  
Cd8 T Cells ◽  
Mucosal Tissues ◽  
Simplex Virus ◽  
Needle Injection ◽  
Hsv 1

Although mucosal surfaces represent the main portal of entry for pathogens, the mechanism of antigen presentation by dendritic cells (DCs) that patrol various mucosal tissues remains unclear. Instead, much effort has focused on the understanding of initiation of immune responses generated against antigens delivered by injection. We examined the contributions of migratory versus lymph node–resident DC populations in antigen presentation to CD4 and CD8 T cells after needle injection, epicutaneous infection, or vaginal mucosal herpes simplex virus (HSV) 1 infection. We show that upon needle injection, HSV-1 became lymph-borne and was rapidly presented by lymph node–resident DCs to CD4 and CD8 T cells. In contrast, after vaginal HSV-1 infection, antigens were largely presented by tissue-derived migrant DCs with delayed kinetics. In addition, migrant DCs made more frequent contact with HSV-specific T cells after vaginal infection compared with epicutaneous infection. Thus, both migrant and resident DCs play an important role in priming CD8 and CD4 T cell responses, and their relative importance depends on the mode of infection in vivo.

scholarly journals Lymph Node Stromal Cells Support Dendritic Cell-Induced Gut-Homing of T Cells

2009 ◽  
Vol 183 (10) ◽  
pp. 6395-6402 ◽  
Author(s):  
Rosalie Molenaar ◽  
Mascha Greuter ◽  
Arnold P. J. van der Marel ◽  
Ramon Roozendaal ◽  
Stefan F. Martin ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
Dendritic Cell ◽  
Stromal Cells ◽  
Lymph Node Stromal Cells

scholarly journals In situ imaging reveals different responses by naïve and memory CD8 T cells to late antigen presentation by lymph node DC after influenza virus infection

2008 ◽  
Vol 38 (12) ◽  
pp. 3304-3315 ◽  
Author(s):  
Kamal M. Khanna ◽  
Carolina C. Aguila ◽  
Jason M. Redman ◽  
Jenny E. Suarez-Ramirez ◽  
Leo Lefrançois ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
Lymph Node ◽  
Virus Infection ◽  
Antigen Presentation ◽  
Cd8 T Cells ◽  
Influenza Virus Infection ◽  
Memory Cd8 T Cells ◽  
Late Antigen
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