Increased Expression of TLR7 in CD8+T Cells Leads to TLR7-Mediated Activation and Accessory Cell-Dependent IFN-γ Production in HIV Type 1 Infection

2009 ◽  
Vol 25 (12) ◽  
pp. 1287-1295 ◽  
Author(s):  
Yang Song ◽  
Yan Zhuang ◽  
Song Zhai ◽  
Dedong Huang ◽  
Ying Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Ifn Γ ◽  
2007 ◽  
Vol 23 (3) ◽  
pp. 427-437 ◽  
Author(s):  
Hanne Gahery ◽  
Suzanne Figueiredo ◽  
Catherine Texier ◽  
Sandra Pouvelle-Moratille ◽  
Lucie Ourth ◽  
...  
Keyword(s):  
T Cells ◽  
Hla Dr ◽  
Ifn Γ ◽  

2010 ◽  
Vol 26 (7) ◽  
pp. 783-793 ◽  
Author(s):  
Sherri L. Surman ◽  
Scott A. Brown ◽  
Bart G. Jones ◽  
David L. Woodland ◽  
Julia L. Hurwitz

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1654-1654
Author(s):  
Young-June Kim ◽  
Hal E. Broxmeyer

Abstract Abstract 1654 Poster Board I-680 CD8+ cytotoxic T cells are often ‘exhausted’ by programmed death-1 (PD-1) signaling, and subsequently the functions of these cells are terminated especially in a tumor environment or upon chronic HIV or HCV infection. Subsets of myeloid cells referred to as myeloid derived suppressor cells (MDSC) or regulatory dendritic cells (DCs) have been implicated in inducing exhaustion or termination of effector CD8+ T cells. To this end, we developed various myeloid-derived dendritic cell (DC) types in vitro from human CD14+ monocytes using M-CSF or GM-CSF in the presence of IL-4 with/without other cytokines, and characterized these DCs with respect to their capacity to induce PD-1 expression on and exhaustion of CD8+ T cells. We then assessed their impact on longevity of CD8+ T cells following coculture. Myeloid DCs developed in vitro with M-CSF and IL-4 for 5 days (referred to as M-DC) did not express ligand for PD-1 (PD-L1) nor did they induce PD-1 on CD8+ T cells. Thus, using M-DCs as starting cells, we sought determinant factors that could modulate M-DCs to express PD-L1 and thereby induce exhaustion of CD8+ T cells. In order to better monitor exhaustion processes, we incubated human peripheral CD8+ T cells for 5 days in the presence of IL-15, an important cytokine for maintaining viability, before coculture. M-DCs showed little impact on exhaustion or longevity of the CD8+ T cells. IL-10 converted M-DC into a distinct myeloid DC subset (referred to as M-DC/IL-10) with an ability to express PD-L1 as well as to induce PD-1 on cocultured CD8+ T cells. M-DC/IL-10 cells markedly suppressed proliferation of cocultured CD8+ T cells. M-DC/IL-10 cells were morphologically unique with many granules and filamentous structures around the cell periphery. These IL-10 effects on M-DC were completely abrogated in the presence of TNF-á. M-DC/IL-10 cells could be further differentiated into another myeloid DC subset in the presence of IFN-γ (referred to as M-DC/IL-10/IFN-γ) with an ability to express even higher levels of PD-L1 compared to M-DC/IL-10 cells. The most remarkable effect of M-DC/IL-10/IFN-γ cells on cocultured CD8+ T cells was a dramatic loss of CD8+ T cells. Light and confocal microscopic observations indicated that loss of CD8+ T cells was due to phagocytosis by M-DC/IL-10/IFN-γ cells. As IFN-γ, a type 1 cytokine which is induced in CD8+ T cells by IL-12 is essential for phagocytosis, we tested whether IL-12 treatment of CD8+ T cells could further enhance phagocytosis induced by M-DC/IL-10/IFN-γ cells. Indeed, IL-12 treatment greatly increased numbers of phagocytosed CD8+ T cells. In contrast, IL-4 treated CD8+ T cells became resistant to phagocytosis, suggesting IFN-γ producing (type1) CD8+ T cells may be primary target cells for the M-DC/IL-10 cells mediated phagocytosis. CD4+ T cells were not as susceptible as CD8+ T cells to phagocytosis. We failed to detect such phagocytic activity induced by prototype DCs generated with GM-CSF and IL-4. Phagocytic activity was not inhibited by various arginase-1 inhibitors suggesting that nitric oxide signaling may not mediate phagocytic activity. Neutralizing antibody to PD-L1 slightly but significantly lowered phagocytic activity suggesting that PD-L1/PD-1 interaction may be partially involved in this process. Myeloid DCs are thought to be immunogenic, actively inducing T cell immune responses. Our results demonstrate that myeloid DCs may play suppressive roles as well through induction of phagocytic activity, especially against IFN-γ producing CD8+ T cells. This may serve as a regulatory mechanism for type 1 CD8+ T cell immune responses in an IL-10 enriched microenvironment. Disclosures No relevant conflicts of interest to declare.


2004 ◽  
Vol 38 (3) ◽  
pp. 412-417 ◽  
Author(s):  
Salvador Resino ◽  
Jose M. Bellon ◽  
M. Dolores Gurbindo ◽  
M. Angeles Munoz‐Fernandez

2014 ◽  
Vol 30 (2) ◽  
pp. 134-141 ◽  
Author(s):  
Chaoyu Xu ◽  
Baochun Ye ◽  
Zongping Han ◽  
Mingxing Huang ◽  
Yujia Zhu

1999 ◽  
Vol 15 (3) ◽  
pp. 265-272 ◽  
Author(s):  
Emiliano N. Mugnaini ◽  
Lise L. Haaheim ◽  
Mette Sannes ◽  
Jan E. Brinchmann

2005 ◽  
Vol 21 (7) ◽  
pp. 620-628 ◽  
Author(s):  
André Inwoley ◽  
Patricia Recordon-Pinson ◽  
Marion Dupuis ◽  
Jessintha Gaston ◽  
Mathieu Genête ◽  
...  
Keyword(s):  
T Cells ◽  

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5655
Author(s):  
Agnieszka Jasiecka-Mikołajczyk ◽  
Jerzy J. Jaroszewski ◽  
Tomasz Maślanka

The purpose of the present study was to broaden the knowledge and understanding of the effects of oclacitinib (OCL), a Janus kinase inhibitor, on T cells in the context of both the immune mechanisms underlying anti-inflammatory and anti-allergic properties of the drug and its safety. The results indicate that beneficial effects of OCL in the treatment of skin allergic diseases may be partially mediated by the inhibition of IL-4 production in CD4+ and CD8+ T cells. To a certain extent, the antiproliferative effect of OCL on CD8+ T cells may also contribute to its therapeutic effect. The study found that OCL does not affect the proliferation of CD4+ T cells or the number of IFN-γ- and IL-17-producing CD4+ and CD8+ T cells. Moreover, OCL was found to counteract the induction of type 1 regulatory T (Tr1) cells and to act as a strong inhibitor of IL-10 production in both CD4+ and CD8+ T cells. Thus, these results indicate that beneficial effects of OCL in the treatment of skin allergic diseases are not mediated through: (a) the abolishment of IFN-γ and IL-17-production in CD4+ and CD8+ T cells; (b) generation of Tr1 cells; (c) inhibition of CD4+ T cell proliferation; (d) induction of IL-10 production in CD4+ T cells. The results of this study strongly suggest that, with respect to the evaluated parameters, OCL exerts a suppressive effect on Th2- but not Th1-mediated immunity.


2012 ◽  
Vol 28 (3) ◽  
pp. 295-298 ◽  
Author(s):  
Agatha Vranjkovic ◽  
Angela M. Crawley ◽  
Jonathan B. Angel

Sign in / Sign up

Export Citation Format

Share Document