scholarly journals Foreign antigen-independent memory-phenotype CD4+ T cells: a new player in innate immunity?

2018 ◽  
Vol 18 (3) ◽  
pp. 1-1 ◽  
Author(s):  
Takeshi Kawabe ◽  
Jinfang Zhu ◽  
Alan Sher
Keyword(s):  
Innate Immunity ◽  
T Cells ◽  
Cd4 T Cells ◽  
Foreign Antigen ◽  
Memory Phenotype

scholarly journals Immunological Aspects of SARS-CoV-2 Infection and the Putative Beneficial Role of Vitamin-D

2021 ◽  
Vol 22 (10) ◽  
pp. 5251
Author(s):  
Ming-Yieh Peng ◽  
Wen-Chih Liu ◽  
Jing-Quan Zheng ◽  
Chien-Lin Lu ◽  
Yi-Chou Hou ◽  
...  
Keyword(s):  
Vitamin D ◽  
Innate Immunity ◽  
T Cells ◽  
Adaptive Immunity ◽  
Cd4 T Cells ◽  
Vitamin D Supplementation ◽  
The Body ◽  
Alveolar Type ◽  
Tissue Destruction ◽  
Health Crisis

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still an ongoing global health crisis. Immediately after the inhalation of SARS-CoV-2 viral particles, alveolar type II epithelial cells harbor and initiate local innate immunity. These particles can infect circulating macrophages, which then present the coronavirus antigens to T cells. Subsequently, the activation and differentiation of various types of T cells, as well as uncontrollable cytokine release (also known as cytokine storms), result in tissue destruction and amplification of the immune response. Vitamin D enhances the innate immunity required for combating COVID-19 by activating toll-like receptor 2. It also enhances antimicrobial peptide synthesis, such as through the promotion of the expression and secretion of cathelicidin and β-defensin; promotes autophagy through autophagosome formation; and increases the synthesis of lysosomal degradation enzymes within macrophages. Regarding adaptive immunity, vitamin D enhances CD4+ T cells, suppresses T helper 17 cells, and promotes the production of virus-specific antibodies by activating T cell-dependent B cells. Moreover, vitamin D attenuates the release of pro-inflammatory cytokines by CD4+ T cells through nuclear factor κB signaling, thereby inhibiting the development of a cytokine storm. SARS-CoV-2 enters cells after its spike proteins are bound to angiotensin-converting enzyme 2 (ACE2) receptors. Vitamin D increases the bioavailability and expression of ACE2, which may be responsible for trapping and inactivating the virus. Activation of the renin–angiotensin–aldosterone system (RAS) is responsible for tissue destruction, inflammation, and organ failure related to SARS-CoV-2. Vitamin D inhibits renin expression and serves as a negative RAS regulator. In conclusion, vitamin D defends the body against SARS-CoV-2 through a novel complex mechanism that operates through interactions between the activation of both innate and adaptive immunity, ACE2 expression, and inhibition of the RAS system. Multiple observation studies have shown that serum concentrations of 25 hydroxyvitamin D are inversely correlated with the incidence or severity of COVID-19. The evidence gathered thus far, generally meets Hill’s causality criteria in a biological system, although experimental verification is not sufficient. We speculated that adequate vitamin D supplementation may be essential for mitigating the progression and severity of COVID-19. Future studies are warranted to determine the dosage and effectiveness of vitamin D supplementation among different populations of individuals with COVID-19.

scholarly journals Early Development in the Peritoneal Cavity of CD49dhigh Th1 Memory Phenotype CD4+ T Cells with Enhanced B Cell Helper Activity

2015 ◽  
Vol 195 (2) ◽  
pp. 564-575 ◽  
Author(s):  
Hana Moon ◽  
Chanho Park ◽  
Jae-Ghi Lee ◽  
Sang Hyuck Shin ◽  
Joo Hee Lee ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Early Development ◽  
Peritoneal Cavity ◽  
Cd4 T Cells ◽  
Memory Phenotype ◽  
Helper Activity

scholarly journals Allergic TH2 Response Governed by B-Cell Lymphoma 6 Function in Naturally Occurring Memory Phenotype CD4+ T Cells

2018 ◽  
Vol 9 ◽  
Author(s):  
Takashi Ogasawara ◽  
Yuko Kohashi ◽  
Jun Ikari ◽  
Toshibumi Taniguchi ◽  
Nobuhide Tsuruoka ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Cd4 T Cells ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Th2 Response ◽  
Memory Phenotype ◽  
Naturally Occurring

IL-21 Gene Modified T Antigen Presenting Cells Enhance the Generation of Tumor-Specific Cytotoxic T Lymphocytes with a Memory Phenotype.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3709-3709
Author(s):  
Anjum S. Kaka ◽  
Ryan Hartmeier ◽  
Ann M. Leen ◽  
An Lu ◽  
Cliona M. Rooney ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cell Cultures ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Antigen Presenting Cells ◽  
Memory Phenotype ◽  
Cytotoxicity Assays ◽  
Antigen Presenting

Abstract IL-21 is a potent cytokine that augments the proliferation and effector function of NK cells and acts in synergy with other γ-chain cytokines to enhance the cytotoxicity of T lymphocytes. IL-21 is transiently produced by activated CD4+ T cells and may facilitate the generation of effector and memory T cells. Recently, T cells have been shown to be effective antigen presenting cells (TAPC) and we hypothesized that this characteristic may be enhanced through overexpression of IL-21 following genetic modification of TAPC. We demonstrate here that transduction of TAPC with IL-21 significantly enhances the generation of MART-1-specific CD8+ T cells suggesting a potential use for IL-21 in tumor immunotherapy protocols. IL-21 was cloned from CD3/CD28-activated CD4+ T cells and inserted into the SFG retroviral vector. To generate IL-21-producing T-APC, CD8-selected T cells from healthy, HLA-A2 donors were stimulated on αCD3/αCD28-coated plates in the presence of IL-2. After 2 days, activated cells were harvested and transduced on Retronectin-coated plates with IL-21 retroviral supernatant. On day 5, TAPC were washed and expanded in growth media supplemented by IL-2. Prior to use as APCs, TAPCs were CD4-depleted by MACS to eliminate residual IL-21 production by CD4+ T cells. IL-21-transduced and non-transduced (NT) CD8+ TAPC pulsed with MART-1 HLA-A2-restricted peptide (ELAGIGILTV) were irradiated and cocultured with autologous CD8+ peripheral blood T cells in media supplemented with IL-7 and IL-12. On day 7, responder T cell cultures were restimulated with peptide-loaded IL-21 or NT CD8+ TAPCs in the presence of IL-2 to induce expansion. Responder T cell cultures were then analyzed for MART-1 specificity by pentamer, ELISPOT and cytotoxicity assays and for their memory phenotype using monoclonal antibodies to CD27, CD28, CD62L, CD45RA, CD45RO, CD127 and CCR7. TAPC were efficiently expanded (>100-fold expansion) and transduced by retrovirus encoding IL-21 (>50% as measured by GFP). Gene modification of TAPC with IL-21 had minimal effect on MHC class I, II, CD80, CD83 and CD86 levels when compared to NT TAPC. However, there was increased expression of CD27, CD28 and CD62L, suggesting that IL-21 was biologically active. Seven days after stimulation with MART-1/ELA peptide-pulsed IL-21-TAPC and NT-TAPC, we observed a substantial increase (10±5-fold) in ELA-specific T cells in cultures stimulated with IL-21-TAPC compared to NT-TAPC when analyzed by FACS using ELA pentamers. Subsequent stimulation with IL-21-TAPCs amplified this effect, resulting in >50-fold increase in absolute ELA-specific T cell numbers when compared to NT-TAPC. ELA-specific CTL generated from IL-21-TAPC stimulation were functional as determined by IFN-γ ELISPOT and cytotoxicity assays. ELA-specific CTL generated from IL-21-TAPC exhibited a unique phenotype (CD45RA−, CD27high, CD28high, CD62Lhigh) as compared to CTL generated form NT-TAPC (CD45RA−, CD27low, CD28low, CD62Llow) suggesting that IL-21 may play a role in the development of T cell memory. In summary, IL-21 enhances the generation of tumor-specific CD8+ T cells which exhibit a central/effector memory phenotype. Our results indicate that IL-21 improves proliferation of antigen-specific T cells, possibly by maintaining CD28 expression allowing costimulation upon secondary antigen encounter.

scholarly journals Egr2 and 3 control inflammation, but maintain homeostasis, of PD-1high memory phenotype CD4 T cells

2020 ◽  
Vol 3 (9) ◽  
pp. e202000766
Author(s):  
Alistair LJ Symonds ◽  
Wei Zheng ◽  
Tizong Miao ◽  
Haiyu Wang ◽  
TieShang Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Cd4 T Cells ◽  
Active Rheumatoid Arthritis ◽  
Inflammatory Responses ◽  
Homeostatic Proliferation ◽  
Adaptive Responses ◽  
Memory Phenotype ◽  
Adaptive Immune ◽  
Cd4 Cell

The transcription factors Egr2 and 3 are essential for controlling inflammatory autoimmune responses of memory phenotype (MP) CD4 T cells. However, the mechanism is still unclear. We have now found that the Egr2+ subset (PD-1high MP) of MP CD4 T cells expresses high levels of checkpoint molecules (PD-1 and Lag3) and also markers of effector T cells (CXCR3 and ICAM-1). Egr2/3 are not required for PD-1high MP CD4 cell development but mediate a unique transcriptional programme that effectively controls their inflammatory responses, while promoting homeostatic proliferation and adaptive responses. Egr2 negative PD-1high MP CD4 T cells are impaired in homeostatic proliferation and adaptive responses against viral infection but display inflammatory responses to innate stimulation such as IL-12. PD-1high MP CD4 T cells have recently been implicated in rheumatoid arthritis pathogenesis, and we have now found that Egr2 expression is reduced in PD-1high MP CD4 T cells from patients with active rheumatoid arthritis compared with healthy controls. These findings demonstrate that Egr2/3 control the inflammatory responses of PD-1high MP CD4 T cells and maintain their adaptive immune fitness.

scholarly journals Alpha Interferon Potently Enhances the Anti-Human Immunodeficiency Virus Type 1 Activity of APOBEC3G in Resting Primary CD4 T Cells

2006 ◽  
Vol 80 (15) ◽  
pp. 7645-7657 ◽  
Author(s):  
Keyang Chen ◽  
Jialing Huang ◽  
Chune Zhang ◽  
Sophia Huang ◽  
Giuseppe Nunnari ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Innate Immunity ◽  
T Cells ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cd4 T Cells ◽  
Immunodeficiency Virus ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACT The interferon (IFN) system, including various IFNs and IFN-inducible gene products, is well known for its potent innate immunity against wide-range viruses. Recently, a family of cytidine deaminases, functioning as another innate immunity against retroviral infection, has been identified. However, its regulation remains largely unknown. In this report, we demonstrate that through a regular IFN-α/β signal transduction pathway, IFN-α can significantly enhance the expression of apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) in human primary resting but not activated CD4 T cells and the amounts of APOBEC3G associated with a low molecular mass. Interestingly, short-time treatments of newly infected resting CD4 T cells with IFN-α will significantly inactivate human immunodeficiency virus type 1 (HIV-1) at its early stage. This inhibition can be counteracted by APOBEC3G-specific short interfering RNA, indicating that IFN-α-induced APOBEC3G plays a key role in mediating this anti-HIV-1 process. Our data suggest that APOBEC3G is also a member of the IFN system, at least in resting CD4 T cells. Given that the IFN-α/APOBEC3G pathway has potent anti-HIV-1 capability in resting CD4 T cells, augmentation of this innate immunity barrier could prevent residual HIV-1 replication in its native reservoir in the post-highly active antiretroviral therapy era.

Age-Related Induction of CD4+ T-Cell Unresponsiveness Is Reversible and Dependant of the Host’s Environment.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3925-3925
Author(s):  
Pedro Horna ◽  
Rahul Chavan ◽  
Jason Brayer ◽  
Ildefonso Suarez ◽  
Eduardo M. Sotomayor
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Cell Compartment ◽  
Memory Phenotype ◽  
Age Related ◽  
And Function

Abstract A large number of CD4+ T-cells from either aged mice or humans display surface markers associated with an activated/memory phenotype. In spite of these changes however, these T-cells have a markedly decreased ability to proliferate and produce IL-2 in response to antigen stimulation in vitro. The cellular and molecular mechanisms involved in this age-related unresponsiveness of the CD4+ T-cell compartment remain poorly understood. Utilizing a well-established experimental system in which transgenic CD4+ T cells specific for a MHC class II restricted epitope of influenza hemagglutinin (HA) are adoptively transferred into non-transgenic recipients, we have previously elucidated important mechanisms involved in the induction and maintenance of CD4+ T-cell tolerance. Our studies were however limited to the analysis of T-cell function in lymphoma bearing young mice (4 to 10 weeks old). Here, we assessed the influence of the aged microenvironment in determining the phenotype and function of antigen-specific T-cells. CD4+ T-cells from young TCR transgenic mice (2 months old) were adoptively transferred into either old (20–24 months) or young (2 months old) non-transgenic mice. Two weeks later, clonotypic and non-clonotypic CD4+ T-cells were isolated from the spleens of these animals and their phenotype and function were determined in vitro. Reminiscent of the age-related changes observed within the normal CD4+ T-cell repertoire, young transgenic T-cells transferred into aged hosts have acquired an activated/memory phenotype but displayed a significant impairment in antigen-specific proliferation and IL-2 production in response to cognate antigen in vitro. These changes were not due to homeostatic proliferation of the transferred T-cells into the relatively lymphopenic aged host. To determine whether the changes observed in “aged” T-cells were reversible or not, we adoptively transfer old T-cells back into young hosts or into control old mice. While old transgenic T-cells transferred into an old environment remained fully unresponsive, the adoptive transfer of the same old T-cells into a young host restored their ability to proliferate and produce IL-2. Surprisingly, these “old” T-cells were able to produce significantly higher levels of IFN-gamma indicative of their memory/effector phenotype. Furthermore, young animals adoptively transferred with “aged” antigen-specific T-cells were now capable of rejecting A20 B-cell lymphomas expressing HA as a model tumor antigen (A20HA). Taking together, factor(s) present in the aged microenvironment are responsible for limiting the effector function of CD4+ T-cells that seem otherwise well equipped to become fully activated if the proper environment is provided (young microenvironment). The potential role of soluble suppressive factors as well as regulatory T-cells (Tregs) in the unresponsiveness observed in the T-cell compartment of aged hosts will be discussed.

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