scholarly journals IL-34- and M-CSF-induced macrophages switch memory T cells into Th17 cells via membrane IL-1α

2015 ◽  
Vol 45 (4) ◽  
pp. 1092-1102 ◽  
Author(s):  
Etienne D. Foucher ◽  
Simon Blanchard ◽  
Laurence Preisser ◽  
Philippe Descamps ◽  
Norbert Ifrah ◽  
...  
Keyword(s):  
T Cells ◽  
Th17 Cells ◽  
Memory T Cells ◽  
Switch Memory

scholarly journals Melatonin Synergizes With Mesenchymal Stromal Cells Attenuates Chronic Allograft Vasculopathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Ya-fei Qin ◽  
De-jun Kong ◽  
Hong Qin ◽  
Yang-lin Zhu ◽  
Guang-ming Li ◽  
...  
Keyword(s):  
T Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Th17 Cells ◽  
Memory T Cells ◽  
Transplant Recipients ◽  
Pathological Changes ◽  
Allograft Vasculopathy

BackgroundChronic rejection characterized by chronic allograft vasculopathy (CAV) remains a major obstacle to long-term graft survival. Due to multiple complicated mechanisms involved, a novel therapy for CAV remains exploration. Although mesenchymal stromal cells (MSCs) have been ubiquitously applied to various refractory immune-related diseases, rare research makes a thorough inquiry in CAV. Meanwhile, melatonin (MT), a wide spectrum of immunomodulator, plays a non-negligible role in transplantation immunity. Here, we have investigated the synergistic effects of MT in combination with MSCs in attenuation of CAV.MethodsC57BL/6 (B6) mouse recipients receiving BALB/c mouse donor aorta transplantation have been treated with MT and/or adipose-derived MSCs. Graft pathological changes, intragraft immunocyte infiltration, splenic immune cell populations, circulating donor-specific antibodies levels, cytokine profiles were detected on post-operative day 40. The proliferation capacity of CD4+ and CD8+ T cells, populations of Th1, Th17, and Tregs were also assessed in vitro.ResultsGrafts in untreated recipients developed a typical pathological feature of CAV characterized by intimal thickening 40 days after transplantation. Compared to untreated and monotherapy groups, MT in combination with MSCs effectively ameliorated pathological changes of aorta grafts indicated by markedly decreased levels of intimal hyperplasia and the infiltration of CD4+ cells, CD8+ cells, and macrophages, but elevated infiltration of Foxp3+ cells. MT either alone or in combination with MSCs effectively inhibited the proliferation of T cells, decreased populations of Th1 and Th17 cells, but increased the proportion of Tregs in vitro. MT synergized with MSCs displayed much fewer splenic populations of CD4+ and CD8+ T cells, Th1 cells, Th17 cells, CD4+ central memory T cells (Tcm), as well as effector memory T cells (Tem) in aorta transplant recipients. In addition, the percentage of splenic Tregs was substantially increased in the combination therapy group. Furthermore, MT combined with MSCs markedly reduced serum levels of circulating allospecific IgG and IgM, as well as decreased the levels of pro-inflammatory IFN-γ, TNF-α, IL-1β, IL-6, IL-17A, and MCP-1, but increased the level of IL-10 in the recipients.ConclusionsThese data suggest that MT has synergy with MSCs to markedly attenuate CAV and provide a novel therapeutic strategy to improve the long-term allograft acceptance in transplant recipients.

scholarly journals Regulation of Antitumor Immune Responses by the IL-12 Family Cytokines, IL-12, IL-23, and IL-27

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Mingli Xu ◽  
Izuru Mizoguchi ◽  
Noriko Morishima ◽  
Yukino Chiba ◽  
Junichiro Mizuguchi ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Th17 Cells ◽  
Antitumor Immunity ◽  
Inflammatory Responses ◽  
Memory T Cells ◽  
Th1 Cells ◽  
Signal Transducers ◽  
Th Cell ◽  
Antigen Presenting

The interleukin (IL)-12 family, which is composed of heterodimeric cytokines including IL-12, IL-23, and IL-27, is produced by antigen-presenting cells such as macrophages and dendritic cells and plays critical roles in the regulation of helper T (Th) cell differentiation. IL-12 induces IFN- production by NK and T cells and differentiation to Th1 cells. IL-23 induces IL-17 production by memory T cells and expands and maintains inflammatory Th17 cells. IL-27 induces the early Th1 differentiation and generation of IL-10-producing regulatory T cells. In addition, these cytokines induce distinct immune responses to tumors. IL-12 activates signal transducers and activator of transcription (STAT)4 and enhances antitumor cellular immunity through interferon (IFN)- production. IL-27 activates STAT1, as does IFN- and STAT3 as well, and enhances antitumor immunity by augmenting cellular and humoral immunities. In contrast, although exogenously overexpressed IL-23 enhances antitumor immunity via memory T cells, endogenous IL-23 promotes protumor immunity through STAT3 activation by inducing inflammatory responses including IL-17 production.

Influence of a mutation in IFN-γ receptor 2 (IFNGR2) in human cells on the generation of Th17 cells in memory T cells

2013 ◽  
Vol 74 (6) ◽  
pp. 693-700 ◽  
Author(s):  
Ursula Holzer ◽  
Katharina Reinhardt ◽  
Peter Lang ◽  
Rupert Handgretinger ◽  
Nadja Fischer
Keyword(s):  
T Cells ◽  
Th17 Cells ◽  
Memory T Cells ◽  
Human Cells ◽  
Ifn Γ

scholarly journals Superantigenic Staphylococcus aureus Stimulates Production of Interleukin-17 from Memory but Not Naive T Cells

2009 ◽  
Vol 78 (1) ◽  
pp. 381-386 ◽  
Author(s):  
Ulrika Islander ◽  
Annica Andersson ◽  
Erika Lindberg ◽  
Ingegerd Adlerberth ◽  
Agnes E. Wold ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
T Cells ◽  
Th17 Cells ◽  
Mononuclear Cells ◽  
Memory T Cells ◽  
Inflammatory Diseases ◽  
Commensal Bacteria ◽  
Interleukin 17 ◽  
T Helper ◽  
T Helper 17

ABSTRACT T-helper 17 (Th17) cells are characterized by their production of interleukin-17 (IL-17) and have a role in the protection against infections and in certain inflammatory diseases. Humans who lack Th17 cells are more susceptible to Staphylococcus aureus infections compared to individuals having Th17 cells. S. aureus is part of the commensal skin microflora and also colonize the infant gut. To investigate whether UV-killed S. aureus would be more capable of inducing IL-17 than other commensal bacteria, we stimulated mononuclear cells from adults, infants, and newborns with various gram-positive and gram-negative commensal bacteria. IL-17 was produced from adult memory Th17 cells after stimulation with superantigen-producing S. aureus but not nonsuperantigenic S. aureus or other common commensal gut bacteria. Cells from newborns were poor IL-17 producers after stimulation with S. aureus, whereas in some cases IL-17 was secreted from cells isolated from infants at the age of 4 and 18 months. These results suggest that superantigenic S. aureus are particularly efficient in stimulating IL-17 production and that the cytokine is produced from memory T cells.

scholarly journals Do Previous Influenza and Mastitis Infections Change the Gene Expressions of Immune T Cell Surface Markers Present in Human Milk?

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 736-736
Author(s):  
Veronique Demers-Mathieu ◽  
Ciera DaPra ◽  
Elena Medo
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
Cell Surface ◽  
Human Milk ◽  
Th17 Cells ◽  
Memory T Cells ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Gene Expressions

Abstract Objectives The function of neonatal T cells is reduced compared to adult T cells. Human milk T cells may be transferred to the breastfed infant and compensate for their immature T cells. This study investigated the impact of mastitis and influenza post-infections (1–4 months) on T cell surface markers’ gene expressions in human milk. Methods Gene expressions of CD4, CD44, CD8A, CCR6, CCR7, CD62L, CXCR3, CXCR5, and CD25 were determined in milk samples from 7 women with mastitis, 7 women with influenza, and 9 women without infection during the last year. The concentrations of Th cytokines (IL-4, IL-17, IFN-g, IL-2, and TNF-b) were also determined. Results The gene expression in milk from women with influenza infection had lower CCR7 (naïve T cells) and higher CD8A (cytotoxic T cells), CD44 and CD62L (activated/memory T cells) than mothers without infection. Gene expression in milk from mothers with mastitis had higher CD4 (Th cells) and lower CCR6 (Th17 cells) than mothers without mastitis. Milk from mothers with previous infections in the past 1–4 months had higher gene expression of CD4, CD8A, CD44, and CD62L, and lower CCR7 and CCR6 (Th17 cells) than mothers without infection. Mastitis or influenza did not affect the concentrations of cytokine-related T cells in human milk, indicating the return to their regular composition of immune regulatory mediators. Conclusions These findings suggest that mothers with previous influenza infections may transfer high human milk-activated/memory T cells to their infants. Whether this transfer of antigen-experienced T cells enhances infants' protection against infection remains to be investigated. Funding Sources The authors (VDM, CD, and ED) disclosed receipt of the financial support from Medolac Laboratories for the conduct of the study.

CD161 Expression Identifies a Distinct Subset Of Drug-Effluxing Viral-Specific Memory CD4+ T Cells That Preferentially Survive Cytotoxic Chemotherapy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2024-2024
Author(s):  
MD Muharrem Muftuoglu ◽  
Abdullah Alsuliman ◽  
Ahmad Khoder ◽  
Yong-Oon Ahn ◽  
Enli Liu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Th17 Cells ◽  
Memory T Cells ◽  
Stem Cell Marker ◽  
Distinct Subset ◽  
Specific Memory ◽  
Memory Cd4 T Cells

Abstract CD4+ T cells are important in the establishment of long-lived pathogen-specific immunity. However, the mechanisms by which antigen specific CD4 T resist insult by lymphocytotoxic agents and are sustained long-term is not well defined. A recent report described the existence of a subset of long-lived CD8+ memory T cells with stem-like properties (Turtle et al, 2009), including the ability to efflux cellular toxins through the ABC–superfamily multidrug efflux protein ABCB1. We hypothesized that a similar subset of T cells with drug-effluxing properties also exists within the CD4+ T cell compartment. We used multiparameter flow cytometry to measure the capacity of CD4+ T cells from donors to efflux the fluorescent substrate Rh123. We identified a subset of memory CD4+ T cells with rapid drug-effluxing ability, defined as CD161+CD95+CD45RA-CD127hiCD28+CD25int that shared remarkable phenotypic similarity to CD8+drug-effluxing memory T cells. The stem cell marker c-kit was preferentially expressed on Rh123 effluxing CD4+CD161+ T cells, whereas CD57, a marker of terminal differentiation, was exclusively expressed on non-effluxing CD4+CD161+ T cells. Rh123 effluxing CD4+CD161+ T cells also displayed differential expression of CD31, CD38, CD58, CD122 and IL-18RA. Rh123 effluxing CD4+ CD161+ T cells were undetectable in cord blood, but found in adult blood, consistent with the emergence of this subset of memory T cells as a consequence of antigen exposure during childhood and adult life. We reasoned that this subset may be enriched within the viral-specific T cell repertoire. Indeed, CMV-specific CD4+ T cells were found to share the same phonotypic markers as Rh123 effluxing CD4+CD161+ T cells. We purified CMV-specific CD4+ T cells using the interferon gamma capture assay (Miltenyi), and showed that CMV-enriched CD4+T cells preferentially and rapidly efflux Rh123. The high ABCB1-mediated drug efflux capacity of CD4+ CD161+ memory cells also facilitated their in vitro resistance to daunorubicin, which was abrogated by competitive inhibitors of ABCB1. In keeping with the in vitro data, we found a significant increase in the frequencies of CMV-specific CD4+ T cells in the peripheral blood of patients with AML after recovery from remission induction chemotherapy, suggesting that CMV-specific CD4+ T cells can preferentially survive and proliferate following chemotherapy. Since interleukin (IL)-7 and IL-15 drive the proliferation of T cells during lymphopenia to restore homeostasis, we assessed the response of CD4+CD161+ T cells to stimulation with CD3/CD28 +IL7 and IL15. Both effluxing and non-effluxing sort-purified central and effector memory CD4+CD161+ T cells proliferated and upregulated Ki67 in vitro. Whereas CD4+CD161+ T cells were able to differentiate into CD4+CD161- T cells, a subset retained CD161 expression. These data suggest that although CD4+CD161+ T cells share phenotypic similarities with terminally differentiated cells, they are able to fully proliferate, differentiate to CD161-ve cells and self-renew to preserve the pool of memory T cells CD161 is also a hallmark of Th17 cells. We examined the cytokine profile of CD4+CD161+ T cells stimulated with a pool of overlapping MHC class II CMV pp65 peptides. After 6 and 24 hrs of in vitro stimulation we failed to detect significant IL-17 production. Furthermore, by real time qPCR, the Th1 transcription factor Tbet, rather than RORC2 (a Th17 hallmark), was found to be preferentially expressed in CMV enriched CD4+CD161+ T cells, indicating that CMV-specific CD4+CD161+T cells in fact represent a unique subset of Th1 cells, distinct from Th17 cells. Our data delineate novel findings related to a distinct subset of drug-effluxing CD4+CD161+ viral-specific memory T cells. Signaling pathways leading to CD4+CD161+ABCB1+ differentiation, the role of this subset in drug resistance and the presence or absence of “stemness” which may impart this subset with extended longevity are being explored. †Muharrem Muftuoglu and Abdullah Alsuliman contributed equally to this work. Disclosures: No relevant conflicts of interest to declare.

Author response for "White matter lesions in multiple sclerosis are enriched for CD20 dim CD8 + tissue‐resident memory T cells"

2020 ◽  
Author(s):  
Cheng‐Chih Hsiao ◽  
Nina L. Fransen ◽  
Aletta M.R. den Bosch ◽  
Kim I.M. Brandwijk ◽  
Inge Huitinga ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
White Matter ◽  
Memory T Cells ◽  
White Matter Lesions ◽  
Author Response ◽  
Resident Memory T Cells
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