Immune Suppression by γδ T-cells as a Potential Regulatory Mechanism After Cancer Vaccination With IL-12 Secreting Dendritic Cells

2010 ◽  
Vol 33 (1) ◽  
pp. 40-52 ◽  
Author(s):  
Michael W. Traxlmayr ◽  
Daniela Wesch ◽  
Alexander M. Dohnal ◽  
Philipp Funovics ◽  
Michael B. Fischer ◽  
...  
Author(s):  
Heather L Chaney ◽  
Lindsay F Grose ◽  
Jeanna M LaBarbara ◽  
Adam W Sirk ◽  
Alyssa M Blancke ◽  
...  

Abstract Conceptus secretory factors include galectins, a family of carbohydrate binding proteins that elicit cell adhesion and immune suppression by interacting with intracellular and extracellular glycans. In rodents, galectin-1 (LGALS1) promotes maternal-fetal immune tolerance in the decidua through expansion of tolerogenic CD11c+ dendritic cells, increased anti-inflammatory IL-10, and activation of FOXP3+ regulatory T cells (Treg). This study characterized galectin expression in early ruminant conceptuses and endometrium. We also tested the effect of recombinant bovine LGALS1 (rbLGALS1) and progesterone (P4) on endometrial expression of genes and protein related to maternal-fetal immune tolerance in cattle. Elongating bovine and ovine conceptuses expressed several galectins, particularly, LGALS1, LGALS3 and LGALS8. Within bovine endometrium, expression of LGALS3, LGALS7 and LGALS9 was greater on Day 16 of pregnancy compared to the estrous cycle. Within ovine endometrium, LGALS7 was greater during pregnancy compared to the estrous cycle and endometrium of pregnant sheep tended to have greater LGALS9 and LGALS15. Expression of endometrial LGALS4 was less during pregnancy in sheep. Treating bovine endometrium with rbLGALS1 increased endometrial expression of CD11c, IL-10 and FOXP3, within 24 h. Specifically, within caruncular endometrium, both rbLGALS1 and P4 increased FOXP3, suggesting that both ligands may promote Treg expansion. Using IHC, FOXP3+ cells with a leukocyte phenotype were localized to the bovine uterine stratum compactum near the uterine surface and increased in response to rbLGALS1. We hypothesize that galectins have important functions during establishment of pregnancy in ruminants and bovine conceptus LGALS1 and luteal P4 confer mechanisms of maternal-conceptus immune tolerance in cattle.


Blood ◽  
2009 ◽  
Vol 114 (20) ◽  
pp. 4422-4431 ◽  
Author(s):  
Georg Gruenbacher ◽  
Hubert Gander ◽  
Andrea Rahm ◽  
Walter Nussbaumer ◽  
Nikolaus Romani ◽  
...  

Abstract CD56+ human dendritic cells (DCs) have recently been shown to differentiate from monocytes in response to GM-CSF and type 1 interferon in vitro. We show here that CD56+ cells freshly isolated from human peripheral blood contain a substantial subset of CD14+CD86+HLA-DR+ cells, which have the appearance of intermediate-sized lymphocytes but spontaneously differentiate into enlarged DC-like cells with substantially increased HLA-DR and CD86 expression or into fully mature CD83+ DCs in response to appropriate cytokines. Stimulation of CD56+ cells containing both DCs and abundant γδ T cells with zoledronate and interleukin-2 (IL-2) resulted in the rapid expansion of γδ T cells as well as in IFN-γ, TNF-α, and IL-1β but not in IL-4, IL-10, or IL-17 production. IFN-γ, TNF-α, and IL-1β production were almost completely abolished by depleting CD14+ cells from the CD56+ subset before stimulation. Likewise, depletion of CD14+ cells dramatically impaired γδ T-cell expansion. IFN-γ production could also be blocked by neutralizing the effects of endogenous IL-1β and TNF-α. Conversely, addition of recombinant IL-1β, TNF-α, or both further enhanced IFN-γ production and strongly up-regulated IL-6 production. Our data indicate that CD56+ DCs from human blood are capable of stimulating CD56+ γδ T cells, which may be harnessed for immunotherapy.


2001 ◽  
Vol 69 (4) ◽  
pp. 2407-2415 ◽  
Author(s):  
M. Lamine Mbow ◽  
Nordin Zeidner ◽  
Robert D. Gilmore ◽  
Marc Dolan ◽  
Joseph Piesman ◽  
...  

ABSTRACT We previously showed that adoptive transfer of Borrelia burgdorferi-pulsed dendritic cells (DCs) into syngeneic mice protects animals from challenge with tick-transmitted spirochetes. Here, we demonstrate that the protective immune response is antibody (Ab) dependent and does not require the presence of major histocompatibility complex (MHC) class II molecules on DCs. Mice sensitized with B. burgdorferi-pulsed MHC class II-deficient (MHC class II−/−) DCs mounted a humoral response against protective antigens, includingB. burgdorferi outer surface protein A (OspA) and OspC. B-cell help for the generation of neutralizing anti-OspC immunoglobulin G Abs could be provided by γδ T cells. In contrast, anti-OspA Ab production required the presence of αβ T cells, although this pathway could be independent of MHC class II molecules on antigen-presenting cells. Moreover, depletion of NK cells prior to transfer of antigen-pulsed MHC class II−/− DCs resulted in significant increases in the levels of neutralizing Abs induced by DCs. Altogether, these data suggest that the initial interactions between DCs and innate immune cells, such as γδ and NK cells, can influence the generation of a protective humoral response againstB. burgdorferi antigens.


2004 ◽  
Vol 174 (1) ◽  
pp. 252-260 ◽  
Author(s):  
Lucia Conti ◽  
Rita Casetti ◽  
Marco Cardone ◽  
Barbara Varano ◽  
Angelo Martino ◽  
...  

2005 ◽  
Vol 175 (9) ◽  
pp. 5656-5665 ◽  
Author(s):  
Cheryl Collins ◽  
Julie Wolfe ◽  
Karen Roessner ◽  
Cuixia Shi ◽  
Leonard H. Sigal ◽  
...  

2007 ◽  
Vol 179 (9) ◽  
pp. 5819-5828 ◽  
Author(s):  
David A. Martin ◽  
Kang Zhang ◽  
Justin Kenkel ◽  
Grant Hughes ◽  
Edward Clark ◽  
...  

2020 ◽  
Author(s):  
Shudong Liu ◽  
jie wang ◽  
Wenyan Li ◽  
Hui Shi ◽  
Changlong Zhou ◽  
...  

Abstract Introduction: TIPE-2 has been identified as a negative regulator of both innate and adaptive immunity and is involved in several inflammatory diseases. However, the role of immune suppression of dendritic cells (DCs) transduced with TIPE-2 has not been well studied. Methods: In this study, DCs were transduced with TIPE-2 recombinant adenovirus, and then were cocultured with allogeneic CD4+ or CD8+T cells. The proliferation, cytokine production and activation marker levels of CD4+ or CD8+T cell were detected. Results: The data demonstrated that T cell proliferation, cytokine production and activation marker levels were attenuated after treated with TIPE-2 transduced DCs. Conclusions: These results suggested that TIPE-2 transduced DCs are capable of inducing allogeneic CD4+ or CD8+T cell immune suppression, which provide a promising way for the therapeutical strategies of transplantation or autoimmune diseases.


2005 ◽  
Vol 202 (2) ◽  
pp. 203-207 ◽  
Author(s):  
Christian Münz ◽  
Ralph M. Steinman ◽  
Shin-ichiro Fujii

Pathogen recognition by Toll-like receptors (TLRs) on dendritic cells (DCs) leads to DC maturation and the initiation of adaptive immunity. Recent studies have shown that innate lymphocytes—natural killer (NK), natural killer T (NKT), and γδ T cells—also trigger DC maturation. This interaction in turn expands and activates innate lymphocytes and initiates adaptive T cell immunity. Here, we comment on the evidence that these pathways are TLR independent and have the potential to respond to infection, malignancy, and immunotherapy.


2021 ◽  
Author(s):  
Mallory Paynich Murray ◽  
Catherine M. Crosby ◽  
Paola Marcovecchio ◽  
Nadine Hartmann ◽  
Shilpi Chandra ◽  
...  

Innate-like T cells, including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells and γδ T cells, are present in various barrier tissues, including the lung. They carry out protective responses during infections, but the mechanisms for protection are not completely understood. Here, we investigated their roles during pulmonary infection with Streptococcus pneumoniae. Following infection, innate-like T cells rapidly increased in lung tissue, in part through recruitment, but TCR activation and cytokine production occurred mostly in IL-17-producing NKT17 and γδ T cells. NKT17 cells were preferentially located outside the vasculature prior to infection, as were CD103+ dendritic cells (cDC1), which were important both for antigen presentation to NKT17 cells and γδ T cell activation. Whereas IL-17A-producing γδ T cells also were numerous, GM-CSF was exclusive to NKT17 cells and contributed to iNKT cell-mediated protection. These studies demonstrate how particular cellular interactions and responses of functional subsets of innate-like T cells contribute to protection from pathogenic lung infection.


2020 ◽  
Author(s):  
Shudong Liu ◽  
jie wang ◽  
Wenyan Li ◽  
Hui Shi ◽  
Changlong Zhou ◽  
...  

Abstract Introduction: TIPE-2 has been identified as a negative regulator of both innate and adaptive immunity and is involved in several inflammatory diseases. However, the role of immune suppression of dendritic cells (DCs) transduced with TIPE-2 has not been well studied. Methods: In this study, DCs were transduced with TIPE-2 recombinant adenovirus, and then were cocultured with allogeneic CD4+ or CD8+T cells. The proliferation, cytokine production and activation marker levels of CD4+ or CD8+T cell were detected. Results: The data demonstrated that T cell proliferation, cytokine production and activation marker levels were attenuated after treated with TIPE-2 transduced DCs. Conclusions: These results suggested that TIPE-2 transduced DCs are capable of inducing allogeneic CD4+ or CD8+T cell immune suppression, which provide a promising way for the therapeutical strategies of transplantation or autoimmune diseases.


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