scholarly journals In Vitro HIV Type 1 Infection Indirectly Alters CD127 Expression on CD8+ T Cells

2012 ◽  
Vol 28 (3) ◽  
pp. 295-298 ◽  
Author(s):  
Agatha Vranjkovic ◽  
Angela M. Crawley ◽  
Jonathan B. Angel
1999 ◽  
Vol 15 (3) ◽  
pp. 265-272 ◽  
Author(s):  
Emiliano N. Mugnaini ◽  
Lise L. Haaheim ◽  
Mette Sannes ◽  
Jan E. Brinchmann

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

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 ◽  

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

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Marcin Moniuszko ◽  
Barbara Glowinska-Olszewska ◽  
Malgorzata Rusak ◽  
Marta Jeznach ◽  
Kamil Grubczak ◽  
...  

Pathobiology of type 1 diabetes (T1D) is predominantly associated with T-cell-related actions. Homeostasis of majority of T-cells is critically dependent on signals mediated by CD127 (interleukin-7 receptor, IL-7R). In contrast, regulatory T-cells express very little CD127 and thereby may be delineated by CD4+CD25+CD127− phenotype. Here we aimed to analyze CD127 expression on CD4+ and CD8+ T-cells and enumerate CD4+CD25+CD127− T-cells in long-lasting T1D. T-cells were analyzed by flow cytometry and immunologic data were correlated with vascular, metabolic, and inflammatory parameters. We demonstrated significantly decreased CD127 levels on CD4+, but not CD8+, T cells in T1D pediatric patients. Interestingly, frequencies of CD4+CD25+CD127− T-cells were significantly enhanced in T1D children and correlated well with frequencies of CD34+CD144+ endothelial progenitor cells and CD4+CD25− T-cells. Levels of CD127 on both CD4+ and CD8+ T-cells in T1D patients were not correlated to each other or HbA1C. Interestingly, however, CD127 levels on CD4+ T-cells were significantly correlated to frequencies of CD4+CD25+CD127− T-cells, whereas CD127 levels on CD8+ T-cells were significantly correlated to concentrations of VEGF and triglycerides. Our data indicate that CD127 expression is differentially modulated on CD4+ and CD8+ T-cells in the course of T1D. Moreover, we demonstrated that, in contrast to recent-onset T1D, long-lasting T1D is associated with enhancement of T-cells with regulatory phenotype.


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

1997 ◽  
Vol 13 (1) ◽  
pp. 79-85 ◽  
Author(s):  
BÅRD RØSOK ◽  
PÅL VOLTERSVIK ◽  
BRITT-MARIE LARSSON ◽  
JAN ALBERT ◽  
JAN E. BRINCHMANN ◽  
...  

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