Tc17, a Unique Subset of CD8 T Cells That Can Protect against Lethal Influenza Challenge

Hamada, Hiromasa; García-Hernández, María de la Luz; Reome, Joyce B.; Misra, Sara K.; Strutt, Tara M.; McKinstry, K. Kai; Cooper, Andrea M.; Swain, Susan L.; Dutton, Richard

doi:10.4049/jimmunol.0801814

Cited by 339 publications

(385 citation statements)

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“…The role of IL-17 as a protective cytokine against lethal influenza challenge and its role in mediating the immunopathology of influenza infection have been reported [28,29]. Hamada et al [28] claimed that IL-17-secreting CD4 T (Th)-17 and CD8 T (Tc)-17 effector cells were present in the lung following primary challenge with influenza A, and reported that a blocking-antibody treatment against IL-17 increased weight loss and reduced survival rate. In reality, the anti-IL-17 antibody studies were only performed in a heterotypic challenge model.…”

Section: Discussionmentioning

confidence: 99%

“…In reality, the anti-IL-17 antibody studies were only performed in a heterotypic challenge model. The authors did not study anti-IL-17 in primary influenza infection, in which nearly all of the IL-17 comes from gamma delta T cells [28]. Crowe et al [29] treated IL-17RA-deficient mice with influenza A, and found that weight loss and survival rates were improved in IL-17RA-deficient mice.…”

Section: Discussionmentioning

confidence: 99%

“…IL-17 has been associated with tissue damage in the brain, joints, heart, lungs and intestines, in experimental models [25][26][27]. However, the role of IL-17 in lung injury induced by influenza is controversial [28][29][30]. Here, the establishment of a suitable mouse model enabled us to directly test whether IL-17 mediates or protects from the acute lung injury induced by 2009 pandemic influenza infection.…”

Section: Il-17-deficient Mice Ameliorated Acute Lung Injury Induced Bmentioning

confidence: 99%

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IL-17 response mediates acute lung injury induced by the 2009 Pandemic Influenza A (H1N1) Virus

et al. 2011

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Il-17-deficient Mice Ameliorated Acute Lung Injury Induced Bmentioning

confidence: 99%

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IL-17 response mediates acute lung injury induced by the 2009 Pandemic Influenza A (H1N1) Virus

et al. 2011

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“…40 Later research has indicated that the response is more nuanced, with some contradictory evidence regarding advantages and disadvantages of IL-17A induction. 41,42,43 Predominance of one set of cytokines over the other is generally indicative of polarization of Th responses, for example the presence of IL-4 and absence of IFN-g indicate a classical Th-2 polarized immune reaction 44 although these cytokines can also be released at the same time. 45,46,47 The varying cytokine profiles related to CTL and antibody production are fundamental in affording protection against a specific pathogen.…”

Section: Respiratory Epithelial Cellsmentioning

confidence: 99%

Current prospects and future challenges for nasal vaccine delivery

Yusuf

Kett

2016

Human Vaccines & Immunotherapeutics

124

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Nasal delivery offers many benefits over traditional approaches to vaccine administration. These include ease of administration without needles that reduces issues associated with needlestick injuries and disposal. Additionally, this route offers easy access to a key part of the immune system that can stimulate other mucosal sites throughout the body. Increased acceptance of nasal vaccine products in both adults and children has led to a burgeoning pipeline of nasal delivery technology. Key challenges and opportunities for the future will include translating in vivo data to clinical outcomes. Particular focus should be brought to designing delivery strategies that take into account the broad range of diseases, populations and healthcare delivery settings that stand to benefit from this unique mucosal route. In this review the current state of the art in nasal vaccine delivery will be described along with future prospects. A brief introduction to the anatomy and physiology of the nasal cavity will highlight the advantages and disadvantages of the route. Encapsulation and presentation methods along with particular formulation considerations for the nasal route will also be discussed.There are many mucosal routes which have been regarded as potential sites for vaccine delivery such as oral, nasal, pulmonary, conjunctival, rectal and vaginal mucosa. However, for practical and cultural reasons researchers have tended to focus only on oral, nasal, and pulmonary administration. 1 Needlefree vaccines offer many advantages over traditional vaccination approaches including convenience, cost, ease of administration and disposal.There are several needle free methods of vaccination such as transdermal delivery and mucosal delivery. 2,3 Mucosal immunization has been successfully used in human vaccination. The human mucosal immune system is large and specialized in performing inspection for foreign antigens to protect the surfaces themselves and of course human body interior. Since most infections affect or start from mucosal surfaces, using a mucosal route of vaccination is of great interest and provides a rational reason to induce a protective immune response. 3 Nasal delivery of vaccine offers an easily accessible route to the immune system.The nose has the function of olfactory detection (sense of smell) and also filtration, humidification and temperature control of air as it enters the respiratory system. Moving from front to back the areas of the nasal cavity are the nasal vestibule, the respiratory region, and the olfactory region. The nasal cavity is divided by the septum to form the left and right nares, which lead into the left and right choana before opening onto the nasopharynx at the top of the throat. The turbinates bound the nasal walls and are responsible for air conditioning and the large mucosal surface area of the nasal cavity. The nose is also the main port of entry for many pathogens. The first barrier to foreign bodies is hair at the entrance to the nares, the nostrils, which successfully keeps ou...

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“…In addition to the cell populations that produce IL-17 in normal conditions and described above, several recent studies have identified the existence of CD8 + T cells expressing IL-17 (Tc17 cells) [14][15][16][17]. Interestingly, Tc17 cells were recently shown to be upregulated in a number of pathological conditions, such as cancer [18][19][20] and acquired immunodeficiency [21,22], suggesting the existence of a dynamic regulatory balance between CD4 + and CD8 + T cells for the production of IL-17.…”

Section: Introductionmentioning

confidence: 99%

Constitutive induction of intestinal Tc17 cells in the absence of hematopoietic cell‐specific MHC class II expression

et al. 2013

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The enteric pathogen Citrobacter rodentium induces a mucosal IL-17 response in CD4 + T helper (Th17) cells that is dependent on the Nod-like receptors Nod1 and Nod2. Here, we sought to determine whether this early Th17 response required antigen presentation by major histocompatibility complex class II (MHCII) for full induction. At early phases of C. rodentium infection, we observed that the intestinal mucosal Th17 response was fully blunted in irradiated mice reconstituted with MHCII-deficient (MHCII −/− →WT) hematopoietic cells. Surprisingly, we also observed a substantial increase in the relative frequency of IL-17 + CD8 + CD4 − TCR-β + cells (Tc17 cells) and FOXP3 + CD8 + CD4 − TCR-β + cells in the lamina propria and intraepithelial lymphocyte compartment of MHCII −/− →WT mice compared with that in WT→WT counterparts. Moreover, MHCII −/− →WT mice displayed increased susceptibility, increased bacterial translocation to deeper organs, and more severe colonic histopathology after infection with C. rodentium. Finally, a similar phenotype was observed in mice deficient for CIITA, a transcriptional regulator of MHCII expression. Together, these results indicate that MHCII is required to mount early mucosal Th17 responses to an enteric pathogen, and that MHCII regulates the induction of atypical CD8 + T-cell subsets, such as Tc17 cells and FOXP3 + CD8 + cells, in vivo. Keywords:Citrobacter rodentium r FOXP3 + CD8 + r IL-17 r MHC class II r Tc17Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionInterleukin (IL)-17A (herein referred to as IL-17) is a cytokine critical for host defense against pathogens at mucosal surfaces. In the gastrointestinal tract, induction of mucosal IL-17 secretion Correspondence: Dr. Stephen E. Girardin e-mail: stephen.girardin@utoronto.ca was shown to be associated with protection against Salmonella enterica serovar Typhymurium [1], Citrobacter rodentium [2], and Helicobacter species [3]. IL-17 exerts its mucosal protection at least in part through an increase of neutrophil recruitment and neutrophil-driven defense mechanisms. In addition, IL-17 acts in concert with IL-22 to enhance epithelial innate functions, such as antimicrobial peptide secretion, mucus secretion, proliferation, and renewal [4,5].IL-17 can be secreted by a number of cell populations, including CD4 + T helper (Th17) cells, γδ T cells, innate lymphoid cells (that C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2013. 43: 2896-2906 Immunity to infection 2897 include lymphoid tissue inducer cells) and natural killer T (NKT) cells [6][7][8][9][10][11]. In humans, Th17 cells appear to represent the major cell population that produces IL-17 in the intestine under normal conditions, whereas in mice IL-17 is mainly produced by Th17 and γδ T cells. Th17 cell differentiation is mediated by the cytokines IL-6 and TGF-β, whereas IL-23 and IL-1β contribute to the full activation of these cells [6,12,13]. In addition to the c...

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Tc17, a Unique Subset of CD8 T Cells That Can Protect against Lethal Influenza Challenge

Cited by 339 publications

References 71 publications

IL-17 response mediates acute lung injury induced by the 2009 Pandemic Influenza A (H1N1) Virus

IL-17 response mediates acute lung injury induced by the 2009 Pandemic Influenza A (H1N1) Virus

Current prospects and future challenges for nasal vaccine delivery

Constitutive induction of intestinal Tc17 cells in the absence of hematopoietic cell‐specific MHC class II expression

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