scholarly journals Recovery of the immune system after exercise

2017 ◽  
Vol 122 (5) ◽  
pp. 1077-1087 ◽  
Author(s):  
Jonathan M. Peake ◽  
Oliver Neubauer ◽  
Neil P. Walsh ◽  
Richard J. Simpson
Keyword(s):  
T Cells ◽  
Immune System ◽  
Cell Function ◽  
Immune Cell ◽  
Physiological Stress ◽  
Current Knowledge ◽  
Ex Vivo ◽  
Γδ T Cells ◽  
Peripheral Tissues ◽  
Recovery Sleep

The notion that prolonged, intense exercise causes an “open window” of immunodepression during recovery after exercise is well accepted. Repeated exercise bouts or intensified training without sufficient recovery may increase the risk of illness. However, except for salivary IgA, clear and consistent markers of this immunodepression remain elusive. Exercise increases circulating neutrophil and monocyte counts and reduces circulating lymphocyte count during recovery. This lymphopenia results from preferential egress of lymphocyte subtypes with potent effector functions [e.g., natural killer (NK) cells, γδ T cells, and CD8+ T cells]. These lymphocytes most likely translocate to peripheral sites of potential antigen encounter (e.g., lungs and gut). This redeployment of effector lymphocytes is an integral part of the physiological stress response to exercise. Current knowledge about changes in immune function during recovery from exercise is derived from assessment at the cell population level of isolated cells ex vivo or in blood. This assessment can be biased by large changes in the distribution of immune cells between blood and peripheral tissues during and after exercise. Some evidence suggests that reduced immune cell function in vitro may coincide with changes in vivo and rates of illness after exercise, but more work is required to substantiate this notion. Among the various nutritional strategies and physical therapies that athletes use to recover from exercise, carbohydrate supplementation is the most effective for minimizing immune disturbances during exercise recovery. Sleep is an important aspect of recovery, but more research is needed to determine how sleep disruption influences the immune system of athletes.

High Activity of Peripheral Blood γδ T Cells in Term and Preterm Neonates.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3897-3897
Author(s):  
Syeda F.Y. Haque ◽  
Deena L. Gibbons ◽  
Katherine Hamilton ◽  
Robert Carr ◽  
Adrian C. Hayday
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Cytokine Production ◽  
Cell Function ◽  
Ex Vivo ◽  
Γδ T Cells ◽  
Preterm Neonates ◽  
Cell Compartment ◽  
Preterm Babies

Abstract The peripheral blood white cell compartment is well characterised in adults but relatively little is known in neonates. T cell function has been reported to be very different between neonates and adults. This is significant because the newborn faces the most precipitous encounter with environmental challenges. To further understand the neonatal T cell compartment, we have focussed on γδ T cells which are known to make essential contributions to the immunoprotection of very young mice. We compared γδ cells and αβ T cells from human cord and neonatal blood from term and preterm babies, and compared them with adults. We investigated T cell cultures ex vivo and derived clones. Several findings were evident. First, we confirmed that fresh neonatal αβ cells and clones are profoundly deficient in IFNγ production. Second, we showed that this is not so pronounced for γδ cells and we note that IFNγ production was higher in preterm babies than in term neonates, perhaps reflective of stress in utero. Neonatal γδ clones also made adult quantities of GM-CSF and TRAIL. We note thirdly that neonatal γδ clones make IL-4 and IL-5 (Th2 cytokines) and the immunosuppressive cytokine IL-10, which is not produced at all by adult Vγ9+ clones. Fourth, these pleiotropic activities of human neonatal γδ clones appears to be determined by the type of T cell receptor expressed. Vδ1-expressing clones have broad functional potentials whereas Vγ9-expressing clones polarise to either a Th1 or Th2 like profile. Fifth, particularly high Th1 cytokine production is observed in Vγ9-Vδ1 (DP) cells which are more common and therefore more easily cloned from neonatal versus adult blood. We conclude that the neonatal γδ cells are highly active and broader in their cytokine production than either their adult γδ cell or their neonatal αβ T cell counterparts. Thus, γδ cells should be better understood vis-à-vis perinatal vaccination regimens and the development of childhood allergies.

scholarly journals Nanoengineering of Immune Cell Function

2009 ◽  
Vol 1209 ◽  
Author(s):  
Keyue Shen ◽  
Michael C Milone ◽  
Michael L. Dustin ◽  
Lance Cameron Kam
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Function ◽  
Immune Cell ◽  
Cell Communication ◽  
Cell Therapies ◽  
Nano Scale

AbstractT lymphocytes are a key regulatory component of the adaptive immune system. Understanding how the micro- and nano-scale details of the extracellular environment influence T cell activation may have wide impact on the use of T cells for therapeutic purposes. In this article, we examine how the micro- and nano-scale presentation of ligands to cell surface receptors, including microscale organization and nanoscale mobility, influences the activation of T cells. We extend these studies to include the role of cell-generated forces, and the rigidity of the microenvironment, on T cell activation. These approaches enable delivery of defined signals to T cells, a step toward understanding the cell-cell communication in the immune system, and developing micro/nano- and material- engineered systems for tailoring immune responses for adoptive T cell therapies.

scholarly journals Small Molecule Inhibitors of MERTK and FLT3 Induce Cell Cycle Arrest in Human CD8+ T Cells

Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1294
Author(s):  
Richard M. Powell ◽  
Marlies J. W. Peeters ◽  
Anne Rahbech ◽  
Pia Aehnlich ◽  
Tina Seremet ◽  
...  
Keyword(s):  
Cell Cycle ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Tyrosine Kinases ◽  
Cell Function ◽  
Immune Cell ◽  
Ex Vivo ◽  
Cell Receptor ◽  
Induce Cell Cycle Arrest

There is an increasing interest in the development of Receptor Tyrosine Kinases inhibitors (RTKIs) for cancer treatment, as dysregulation of RTK expression can govern oncogenesis. Among the newer generations of RTKIs, many target Mer Tyrosine Kinase (MERTK) and Fms related RTK 3 (FLT3). Next to being overexpressed in many cancers, MERTK and FLT3 have important roles in immune cell development and function. In this study, we address how the new generation and potent RTKIs of MERTK/FLT3 affect human primary CD8+ T cell function. Using ex vivo T cell receptor (TCR)-activated CD8+ T cells, we demonstrate that use of dual MERTK/FLT3 inhibitor UNC2025 restricts CD8+ T proliferation at the G2 phase, at least in part by modulation of mTOR signaling. Cytokine production and activation remain largely unaffected. Finally, we show that activated CD8+ T cells express FLT3 from day two post activation, and FLT3 inhibition with AC220 (quizartinib) or siRNA-mediated knockdown affects cell cycle kinetics. These results signify that caution is needed when using potent RTKIs in the context of antitumor immune responses.

scholarly journals Human Tissue-Resident Memory T Cells in the Maternal–Fetal Interface. Lost Soldiers or Special Forces?

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2699
Author(s):  
Caitlin S. DeJong ◽  
Nicholas J. Maurice ◽  
Stephen A. McCartney ◽  
Martin Prlic
Keyword(s):  
T Cells ◽  
Immune System ◽  
Cell Function ◽  
Immune Cell ◽  
Memory T Cells ◽  
Critical Role ◽  
Immune Cell Function ◽  
Histocompatibility Complex ◽  
Resident Memory T Cells ◽  
Maternal Fetal Interface

The immune system plays a critical role during pregnancy, but the specific mechanisms and immune cell function needed to support pregnancy remain incompletely understood. Despite decades of research efforts, it is still unclear how the immune system maintains tolerance of fetal-derived tissues, which include most cells of the placenta and of course the fetus itself, without forfeiting the ability to protect against harmful infections. T cells recognize antigen in the context of major histocompatibility complex (MHC) encoded proteins, but classical MHC class I and II expression are diminished in fetal-derived cells. Can T cells present at the maternal–fetal interface (MFI) protect these cells from infection? Here we review what is known in regard to tissue-resident memory T (Trm) cells at the MFI. We mainly focus on how Trm cells can contribute to protection in the context of the unique features of the MFI, such as limited MHC expression as well as the temporary nature of the MFI, that are not found in other tissues.

scholarly journals Epigenetic Modifications in T Cells

Hypertension ◽  
2020 ◽  
Vol 75 (2) ◽  
pp. 372-382 ◽  
Author(s):  
John Henry Dasinger ◽  
Ammar J. Alsheikh ◽  
Justine M. Abais-Battad ◽  
Xiaoqing Pan ◽  
Daniel J. Fehrenbach ◽  
...  
Keyword(s):  
Dna Methylation ◽  
T Cells ◽  
Immune System ◽  
Renal Damage ◽  
Cell Function ◽  
Immune Cell ◽  
Dna Methyltransferases ◽  
Epigenetic Modifications ◽  
High Salt ◽  
Immune System Activation

The SS (Dahl salt sensitive) rat is an established model of hypertension and renal damage that is accompanied with immune system activation in response to a high-salt diet. Investigations into the effects of sodium-independent and dependent components of the diet were shown to affect the disease phenotype with SS/MCW (JrHsdMcwi) rats maintained on a purified diet (AIN-76A) presenting with a more severe phenotype relative to grain-fed SS/CRL (JrHsdMcwiCrl) rats. Since contributions of the immune system, environment, and diet are documented to alter this phenotype, this present study examined the epigenetic profile of T cells isolated from the periphery and the kidney from these colonies. T cells isolated from kidneys of the 2 colonies revealed that transcriptomic and functional differences may contribute to the susceptibility of hypertension and renal damage. In response to high-salt challenge, the methylome of T cells isolated from the kidney of SS/MCW exhibit a significant increase in differentially methylated regions with a preference for hypermethylation compared with the SS/CRL kidney T cells. Circulating T cells exhibited similar methylation profiles between colonies. Utilizing transcriptomic data from T cells isolated from the same animals upon which the DNA methylation analysis was performed, a predominant negative correlation was observed between gene expression and DNA methylation in all groups. Lastly, inhibition of DNA methyltransferases blunted salt-induced hypertension and renal damage in the SS/MCW rats providing a functional role for methylation. This study demonstrated the influence of epigenetic modifications to immune cell function, highlighting the need for further investigations.

scholarly journals The Aging of γδ T Cells

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1181 ◽  
Author(s):  
Weili Xu ◽  
Zandrea Wan Xuan Lau ◽  
Tamas Fulop ◽  
Anis Larbi
Keyword(s):  
T Cells ◽  
Immune System ◽  
Immune Cell ◽  
Γδ T Cells ◽  
Cell Types ◽  
Developed Countries ◽  
Common Denominator ◽  
Age Related ◽  
The Relationship ◽  
Diverse Interactions

In the coming decades, many developed countries in the world are expecting the “greying” of their populations. This phenomenon poses unprecedented challenges to healthcare systems. Aging is one of the most important risk factors for infections and a myriad of diseases such as cancer, cardiovascular and neurodegenerative diseases. A common denominator that is implicated in these diseases is the immune system. The immune system consists of the innate and adaptive arms that complement each other to provide the host with a holistic defense system. While the diverse interactions between multiple arms of the immune system are necessary for its function, this complexity is amplified in the aging immune system as each immune cell type is affected differently—resulting in a conundrum that is especially difficult to target. Furthermore, certain cell types, such as γδ T cells, do not fit categorically into the arms of innate or adaptive immunity. In this review, we will first introduce the human γδ T cell family and its ligands before discussing parallels in mice. By covering the ontogeny and homeostasis of γδ T cells during their lifespan, we will better capture their evolution and responses to age-related stressors. Finally, we will identify knowledge gaps within these topics that can advance our understanding of the relationship between γδ T cells and aging, as well as age-related diseases such as cancer.

scholarly journals RhoA as a Key Regulator of Innate and Adaptive Immunity

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 733 ◽  
Author(s):  
Bros ◽  
Haas ◽  
Moll ◽  
Grabbe
Keyword(s):  
T Cells ◽  
Immune System ◽  
Immune Cell ◽  
Immunological Synapse ◽  
Current Knowledge ◽  
Adaptive Immune System ◽  
Cell Types ◽  
Small Gtpases ◽  
Cytoskeletal Proteins ◽  
Effector Cells

RhoA is a ubiquitously expressed cytoplasmic protein that belongs to the family of small GTPases. RhoA acts as a molecular switch that is activated in response to binding of chemokines, cytokines, and growth factors, and via mDia and the ROCK signaling cascade regulates the activation of cytoskeletal proteins, and other factors. This review aims to summarize our current knowledge on the role of RhoA as a general key regulator of immune cell differentiation and function. The contribution of RhoA for the primary functions of innate immune cell types, namely neutrophils, macrophages, and conventional dendritic cells (DC) to (i) get activated by pathogen-derived and endogenous danger signals, (ii) migrate to sites of infection and inflammation, and (iii) internalize pathogens has been fairly established. In activated DC, which constitute the most potent antigen-presenting cells of the immune system, RhoA is also important for the presentation of pathogen-derived antigen and the formation of an immunological synapse between DC and antigen-specific T cells as a prerequisite to induce adaptive T cell responses. In T cells and B cells as the effector cells of the adaptive immune system Rho signaling is pivotal for activation and migration. More recently, mutations of Rho and Rho-modulating factors have been identified to predispose for autoimmune diseases and as causative for hematopoietic malignancies.

scholarly journals Pregnancy-Associated Alterations of Peripheral Blood Immune Cell Numbers in Domestic Sows Are Modified by Social Rank

Animals ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 112
Author(s):  
Christiane Schalk ◽  
Birgit Pfaffinger ◽  
Sonja Schmucker ◽  
Ulrike Weiler ◽  
Volker Stefanski
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Plasma Cortisol ◽  
Immune Cell ◽  
Cytotoxic T Cells ◽  
Social Rank ◽  
Γδ T Cells ◽  
Detailed Knowledge ◽  
Immune Functions

During pregnancy, the maternal immune system is characterized by a shift from adaptive to innate immune functions. Besides, the immune system can be influenced by social rank. Detailed knowledge of pregnancy-associated immune changes and of the interplay of rank-associated and gestation-induced immunomodulations is still fragmentary in sows. This study investigates both the numbers of various blood leukocyte subpopulations during pregnancy and the influence of social rank position on progressing pregnancy-associated alterations in group-housed sows. Sows were classified as low (LR), middle (MR), or high-ranking (HR). Five blood samples were collected from each of the 35 sows throughout pregnancy to evaluate the distribution of blood lymphocyte subpopulations and plasma cortisol concentrations. The numbers of T, natural killer (NK), and B cells, cytotoxic T cells (CTL), and CD8+ γδ- T cells decreased during the last trimester of pregnancy, while neutrophils and plasma cortisol concentration increased before parturition. Social rank revealed different effects on B cells and monocytes with MR sows showing higher numbers than LR sows. Plasma cortisol concentrations also tended to be higher in MR sows as compared to LR sows. In conclusion, sows show pregnancy-associated alterations in the immune system, which are influenced by social rank, as middle-ranking sows in particular display signs of stress-induced immunomodulations.

scholarly journals Chronic low-level cadmium exposure in rats affects cytokine production by activated T cells

2019 ◽  
Vol 8 (2) ◽  
pp. 227-237 ◽  
Author(s):  
Alexandra E. Turley ◽  
Joseph W. Zagorski ◽  
Rebekah C. Kennedy ◽  
Robert A. Freeborn ◽  
Jenna K. Bursley ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Low Dose ◽  
Cytokine Production ◽  
Ex Vivo ◽  
Cadmium Exposure ◽  
Activated T Cells ◽  
Low Level

The purpose of this study was to determine the effect of subchronic, oral, low-dose cadmium exposure (32 ppm over 10 weeks) on the rat immune system. We found that cadmium exposure increased the induction of IFNγ and IL-10 in T cells activated ex vivo after cadmium exposure.

scholarly journals 602 STING agonist-based treatment promotes vascular normalization and tertiary lymphoid structure formation in the therapeutic melanoma microenvironment

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A637-A637
Author(s):  
Manoj Chelvanambi ◽  
Ronald Fecek ◽  
Jennifer Taylor ◽  
Walter Storkus
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Immune Cell ◽  
Ex Vivo ◽  
In Vitro Assays ◽  
Type I ◽  
Vascular Normalization ◽  
S 100 ◽  
Transcriptional Changes

BackgroundThe degree of immune infiltration in tumors, especially CD8+ T cells, greatly impacts patient disease course and response to interventional immunotherapy. Hence, enhancement of TIL prevalence is a preferred clinical endpoint, one that may be achieved via administration of agents that normalize the tumor vasculature (VN) leading to improved immune cell recruitment and/or that induce the development of local tertiary lymphoid structures (TLS) within the tumor microenvironment (TME).MethodsLow-dose STING agonist ADU S-100 (5 μg/mouse) was delivered intratumorally to established s.c. B16.F10 melanomas on days 10, 14 and 17 post-tumor inoculation under an IACUC-approved protocol. Treated and control, untreated tumors were isolated at various time points to assess transcriptional changes associated with VN and TLS formation via qPCR, with corollary immune cell composition changes determined using flow cytometry and immunofluorescence microscopy. In vitro assays were performed on CD11c+ BMDCs treated with 2.5 μg/mL ADU S-100 (vs PBS control) and associated transcriptional changes analyzed via qPCR or profiled using DNA microarrays. For TCRβ-CDR3 analyses, CDR3 was sequenced from gDNA isolated from enzymatically digested tumors and splenocytes.ResultsWe report that activation of STING within the TME leads to slowed melanoma growth in association with increased production of angiostatic factors including Tnfsf15 (Vegi), Cxcl10 and Angpt1, and TLS inducing factors including Ccl19, Ccl21, Lta, Ltb and Tnfsf14 (Light). Therapeutic responses from intratumoral STING activation were characterized by increased vascular normalization (VN), enhanced tumor infiltration by CD8+ T cells and CD11c+ DCs and local TLS neo-genesis, all of which were dependent on host expression of STING. Consistent with a central role for DC in TLS formation, ex vivo ADU S-100-activated mCD11c+ DCs also exhibited upregulated expression of TLS promoting factors including lymphotoxin-α (LTA), IL-36, inflammatory chemokines and type I interferons. TLS formation was associated with the development of a therapeutic TIL TCR repertoire enriched in T cell clonotypes uniquely detected within the tumor but not the peripheral circulation in support or local T cell cross-priming within the TME.ConclusionsOur data support the premise that i.t. delivery of STING agonist promotes a pro-inflammatory TME in support of VN and TLS formation, leading to the local expansion of unique TIL repertoire in association with superior anti-melanoma efficacy.

Sign in / Sign up

Export Citation Format

Share Document