scholarly journals Infection-Induced Dermal Lymphatic Zippering Restricts Viral Dissemination from Skin and Promotes Anti-Viral CD8+ T Cell Expansion

2021 ◽  
Author(s):  
Madeline J. Churchill ◽  
Haley du Bois ◽  
Taylor A. Heim ◽  
Tenny Mudianto ◽  
Maria M. Steele ◽  
...  
Keyword(s):  
T Cell ◽  
Lymph Nodes ◽  
Vaccinia Virus ◽  
Host Defense ◽  
Lymphatic Vessels ◽  
T Cell Responses ◽  
Lymphatic Capillary ◽  
Viral Dissemination ◽  
Cell Responses ◽  
Draining Lymph Nodes

AbstractLymphatic vessels are often considered passive conduits that rapidly flush antigenic material, pathogens, and cells to draining lymph nodes. Recent evidence, however, suggests that lymphatic vessels actively regulate diverse processes from antigen transport to leukocyte trafficking and dietary lipid absorption. Here we tested the hypothesis that dermal lymphatic transport is dynamic and contributes to innate host defense during viral infection. We demonstrate that cutaneous vaccinia virus infection activates the tightening of lymphatic interendothelial junctions, termed zippering, in a VEGFA/VEGFR2-dependent manner. Both antibody-mediated blockade of VEGFA/VEGFR2 and lymphatic-specific deletion of Vegfr2 impaired lymphatic capillary zippering and increased fluid flux out of tissue. Strikingly, inhibition of lymphatic zippering allows viral dissemination to draining lymph nodes independent of dendritic cell migration and impairs CD8+ T cell priming. These data indicate that infection-induced dermal lymphatic capillary zippering is a context-dependent, active mechanism of innate host defense that limits interstitial fluid and virion flux and promotes protective, anti-viral CD8+ T cell responses.SummaryCutaneous infection with vaccinia virus induces VEGFR2-dependent dermal lymphatic capillary zippering. This tightening of lymphatic junctions exacerbates tissue edema, sequesters virus, and promotes anti-viral CD8+ T cell responses. Dermal lymphatic capillaries are therefore an active component of innate host defense.

scholarly journals Natural killer cells recruited into lymph nodes inhibit alloreactive T-cell activation through perforin-mediated killing of donor allogeneic dendritic cells

Blood ◽  
2008 ◽  
Vol 112 (3) ◽  
pp. 661-671 ◽  
Author(s):  
Sophie Laffont ◽  
Cyril Seillet ◽  
John Ortaldo ◽  
Jérôme D. Coudert ◽  
Jean-Charles Guéry
Keyword(s):  
T Cell ◽  
Lymph Nodes ◽  
Nk Cells ◽  
Nk Cell ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Alloreactive T Cell ◽  
Draining Lymph Nodes

Abstract Natural killer (NK)–cell alloreactivity is exploited in bone marrow transplantation to improve clinical outcome. Likewise, in solid organ transplantation, it has been recently shown that recipient NK cells may limit alloreactive T-cell responses through their capacity to prevent the persistence of graft-derived allogeneic dendritic cells (DCs). In a model of CD4+ T cell–mediated allogeneic skin graft rejection, we show that the absence of host NK-cell alloreactivity was characterized by enhanced expansion of alloreactive effector T lymphocytes, including Th2 cells, and massive eosinophilic infiltrates in the rejected tissues. In CD8+ T cell–deficient C57BL/6 (H-2b) recipients injected with allogeneic BALB/c (H-2d) DCs, we demonstrated that NK cells expressing the H-2Dd-specific Ly49D activating receptor were implicated in the regulation of alloreactive CD4+ T-cell responses. Moreover, we showed that Ly49D+ CD127− NK cells were recruited within DC draining lymph nodes and rapidly eliminated allogeneic H-2d DCs through the perforin pathway. In normal mice, we further demonstrated that NK cells by quickly eliminating allogeneic DCs strongly inhibited alloreactive CD8+ T-cell responses. Thus, NK cells act as early regulators of alloreactive T-cell priming in allotransplantation through their capacity to kill allogeneic DCs in draining lymph nodes.

Different-Sized Gold Nanoparticle Activator/Antigen Increases Dendritic Cells Accumulation in Liver-Draining Lymph Nodes and CD8+ T Cell Responses

ACS Nano ◽  
2016 ◽  
Vol 10 (2) ◽  
pp. 2678-2692 ◽  
Author(s):  
Qianqian Zhou ◽  
Yulong Zhang ◽  
Juan Du ◽  
Yuan Li ◽  
Yong Zhou ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Gold Nanoparticle ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Draining Lymph Nodes

Anti-CTLA-4 antibody-functionalized dendritic cell-derived exosomes targeting tumor-draining lymph nodes for effective induction of antitumor T-cell responses

2020 ◽  
Vol 115 ◽  
pp. 371-382 ◽  
Author(s):  
Cao Dai Phung ◽  
Thanh Tung Pham ◽  
Hanh Thuy Nguyen ◽  
Tien Tiep Nguyen ◽  
Wenquan Ou ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
Lymph Nodes ◽  
T Cell Responses ◽  
Cell Responses ◽  
Draining Lymph Nodes

scholarly journals Neutrophil subtypes shape HIV-specific CD8 T-cell responses after vaccinia virus infection

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Mauro Di Pilato ◽  
Miguel Palomino-Segura ◽  
Ernesto Mejías-Pérez ◽  
Carmen E. Gómez ◽  
Andrea Rubio-Ponce ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Vaccinia Virus ◽  
Adaptive Immune System ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Adaptive Immune

AbstractNeutrophils are innate immune cells involved in the elimination of pathogens and can also induce adaptive immune responses. Nα and Nβ neutrophils have been described with distinct in vitro capacity to generate antigen-specific CD8 T-cell responses. However, how these cell types exert their role in vivo and how manipulation of Nβ/Nα ratio influences vaccine-mediated immune responses are not known. In this study, we find that these neutrophil subtypes show distinct migratory and motility patterns and different ability to interact with CD8 T cells in the spleen following vaccinia virus (VACV) infection. Moreover, after analysis of adhesion, inflammatory, and migration markers, we observe that Nβ neutrophils overexpress the α4β1 integrin compared to Nα. Finally, by inhibiting α4β1 integrin, we increase the Nβ/Nα ratio and enhance CD8 T-cell responses to HIV VACV-delivered antigens. These findings provide significant advancements in the comprehension of neutrophil-based control of adaptive immune system and their relevance in vaccine design.

scholarly journals Batf3-Dependent Dendritic Cells Promote Optimal CD8 T Cell Responses against Respiratory Poxvirus Infection

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Pritesh Desai ◽  
Vikas Tahiliani ◽  
Georges Abboud ◽  
Jessica Stanfield ◽  
Shahram Salek-Ardakani
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Vaccinia Virus ◽  
Respiratory Infection ◽  
Host Resistance ◽  
T Cell Responses ◽  
Cell Responses ◽  
Ifn Γ ◽  
The Impact

ABSTRACTRespiratory infection with vaccinia virus (VacV) elicits robust CD8+T cell responses that play an important role in host resistance. In the lung, VacV encounters multiple tissue-resident antigen-presenting cell (APC) populations, but which cell plays a dominant role in priming of virus-specific CD8+effector T cell responses remains poorly defined. We used Batf3−/−mice to investigate the impact of CD103+and CD8α+dendritic cell (DC) deficiency on anti-VacV CD8+T cell responses. We found that Batf3−/−mice were more susceptible to VacV infection, exhibiting profound weight loss, which correlated with impaired accumulation of gamma interferon (IFN-γ)-producing CD8+T cells in the lungs. This was largely due to defective priming since early in the response, antigen-specific CD8+T cells in the draining lymph nodes of Batf3−/−mice expressed significantly reduced levels of Ki67, CD25, and T-bet. These results underscore a specific role for Batf3-dependent DCs in regulating priming and expansion of effector CD8+T cells necessary for host resistance against acute respiratory VacV infection.IMPORTANCEDuring respiratory infection with vaccinia virus (VacV), a member ofPoxviridaefamily, CD8+T cells play important role in resolving the primary infection. Effector CD8+T cells clear the virus by accumulating in the infected lungs in large numbers and secreting molecules such as IFN-γ that kill virally infected cells. However, precise cell types that regulate the generation of effector CD8+T cells in the lungs are not well defined. Dendritic cells (DCs) are a heterogeneous population of immune cells that are recognized as key initiators and regulators of T-cell-mediated immunity. In this study, we reveal that a specific subset of DCs that are dependent on the transcription factor Batf3 for their development regulate the magnitude of CD8+T cell effector responses in the lungs, thereby providing protection during pulmonary VacV infection.

scholarly journals Inducible Bronchus-Associated Lymphoid Tissue (iBALT) Synergizes with Local Lymph Nodes during Antiviral CD4+ T Cell Responses

2013 ◽  
Vol 11 (4) ◽  
pp. 196-202 ◽  
Author(s):  
Laura E. Richert ◽  
Ann L. Harmsen ◽  
Agnieszka Rynda-Apple ◽  
James A. Wiley ◽  
Amy E. Servid ◽  
...  
Keyword(s):  
T Cell ◽  
Lymph Nodes ◽  
Lymphoid Tissue ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Responses

scholarly journals Innate cell microenvironments in lymph nodes shape the generation of T cell responses during type I inflammation

2021 ◽  
Vol 6 (56) ◽  
pp. eabb9435
Author(s):  
Joseph M. Leal ◽  
Jessica Y. Huang ◽  
Karan Kohli ◽  
Caleb Stoltzfus ◽  
Miranda R. Lyons-Cohen ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Lymph Nodes ◽  
Critical Role ◽  
Myeloid Cell ◽  
T Cell Responses ◽  
Type I ◽  
Cell Responses ◽  
Inflammatory Monocytes ◽  
Cell Effector

Microanatomical organization of innate immune cells within lymph nodes (LNs) is critical for the generation of adaptive responses. In particular, steady-state LN-resident dendritic cells (Res cDCs) are strategically localized to intercept lymph-draining antigens. Whether myeloid cell organization changes during inflammation and how that might affect the generation of immune responses are unknown. Here, we report that during type I, but not type II, inflammation after adjuvant immunization or viral infection, antigen-presenting Res cDCs undergo CCR7-dependent intranodal repositioning from the LN periphery into the T cell zone (TZ) to elicit T cell priming. Concurrently, inflammatory monocytes infiltrate the LNs via local blood vessels, enter the TZ, and cooperate with Res cDCs by providing polarizing cytokines to optimize T cell effector differentiation. Monocyte infiltration is nonuniform across LNs, generating distinct microenvironments with varied local innate cell composition. These spatial microdomains are associated with divergent early T cell effector programming, indicating that innate microenvironments within LNs play a critical role in regulating the quality and heterogeneity of T cell responses. Together, our findings reveal that dynamic modulation of innate cell microenvironments during type I inflammation leads to optimized generation of adaptive immune responses to vaccines and infections.

scholarly journals Immediate-Early Expression of a Recombinant Antigen by Modified Vaccinia Virus Ankara Breaks the Immunodominance of Strong Vector-Specific B8R Antigen in Acute and Memory CD8 T-Cell Responses

2010 ◽  
Vol 84 (17) ◽  
pp. 8743-8752 ◽  
Author(s):  
Karen Baur ◽  
Kay Brinkmann ◽  
Marc Schweneker ◽  
Juliane Pätzold ◽  
Christine Meisinger-Henschel ◽  
...  
Keyword(s):  
T Cell ◽  
Vaccinia Virus ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Immediate Early ◽  
Egfp Expression ◽  
Cell Responses ◽  
Modified Vaccinia Virus Ankara ◽  
Memory Cd8 T Cell ◽  
Early Late

ABSTRACT Efficient T-cell responses against recombinant antigens expressed by vaccinia virus vectors require expression of these antigens in the early phase of the virus replication cycle. The kinetics of recombinant gene expression in poxviruses are largely determined by the promoter chosen. We used the highly attenuated modified vaccinia virus Ankara (MVA) to determine the role of promoters in the induction of CD8 T-cell responses. We constructed MVA recombinants expressing either enhanced green fluorescent protein (EGFP) or chicken ovalbumin (OVA), each under the control of a hybrid early-late promoter (pHyb) containing five copies of a strong early element or the well-known early-late p7.5 or pS promoter for comparison. In primary or cultured cells, EGFP expression under the control of pHyb was detected within 30 min, as an immediate-early protein, and remained higher over the first 6 h of infection than p7.5- or pS-driven EGFP expression. Repeated immunizations of mice with recombinant MVA expressing OVA under the control of the pHyb promoter led to superior acute and memory CD8 T-cell responses compared to those to p7.5- and pS-driven OVA. Moreover, OVA expressed under the control of pHyb replaced the MVA-derived B8R protein as the immunodominant CD8 T-cell antigen after three or more immunizations. This is the first demonstration of an immediate-early neoantigen expressed by a poxviral vector resulting in superior induction of neoantigen-specific CD8 T-cell responses.

Sign in / Sign up

Export Citation Format

Share Document