T-Lymphocyte Activation is Not Affected by the Mobilization of Senescent T-Cells into the Peripheral Blood Following an Acute Bout of Exercise

It is well recognized that individuals are at an increased risk of illness following an arduous exercise regime. Exercise may affect activation status of cells and play a pivotal role in defense against pathogenic invasion. CD69 is the earliest known expressed cell surface antigen of T-cell activation and is a reliable marker of cell activation status (Green et al. Med. Sci. Sports Exerc. 35, 582-588: 2003). Exercise is known to alter the frequency of senescent cells in the blood expressing the cell surface glycoprotein killer cell lectin-like receptor G1 (KLRG1), and are antigen-experienced and unable to clonally expand upon further antigenic stimulation (Simpson et al. J. Appl. Phys. 103, 396-401:2007), PURPOSE: To examine the contribution of senescent T-cells mobilized by exercise on the overall activation status of the peripheral blood T-cell pool following an acute bout of exercise. METHODS: Ten moderately trained males (age: 24.6 ± 4.8; height: 183.1 ± 6.7cm; mass: 72.8 ± 7.9kg; ; 61.3 ± 5.9 ml.kg-1.min-1) ran at speeds corresponding to 80% until volitional exhaustion (time: 36.1 ± 5.8 minutes). Blood lymphocytes isolated before (PRE), immediately after (POST) and 1 hour after (1HrPOST) exercise were stimulated for 4 hours in culture with and without the mitogen PMA and assessed for KLRG1 and CD69 expression and co-expression on CD3+, CD3+/CD4+ (CD4+) and CD3+/CD8+ (CD8+) lymphocyte subsets using 4-colour flow cytometry. RESULTS: No changes in CD69 GMFI were observed on total CD3+, CD4+ and CD8+ T-cells POST or 1HrPOST exercise. The proportions of KLRG1+ cells among the total CD3+, CD4+ and CD8+ T-cell populations increased by 172%, 107% and 169% respectively POST exercise and fell below baseline values 1h later (p\u3c0.05). At all sample time points, CD69 GMFI was greater on stimulated KLRG1+ T-cells compared to KLRG1- cells (p\u3c0.05). CONCLUSION: We conclude that exercise does not affect the activation status of the total T-cell pool. Instead, the number of senescent cells expressing CD69 is greater than those that are not senescent at all times. This suggests that upon pathogenic invasion post-exercise

Chronic HCV Infection Affects the NK Cell Phenotype in the Blood More than in the Liver

Although epidemiological and functional studies have implicated NK cells in protection and early clearance of HCV, the mechanism by which they may contribute to viral control is poorly understood, particularly at the site of infection, the liver. We hypothesized that a unique immunophenotypic/functional NK cell signature exists in the liver that may provide insights into the contribution of NK cells to viral control. Intrahepatic and blood NK cells were profiled from chronically infected HCV-positive and HCV-negative individuals. Baseline expression of activating and inhibitory receptors was assessed, as well as functional responses following stimulation through classic NK cell pathways. Independent of HCV infection, the liver was enriched for the immunoregulatory CD56bright NK cell population, which produced less IFNγ and CD107a but comparable levels of MIP1β, and was immunophenotypically distinct from their blood counterparts. This profile was mostly unaltered in chronic HCV infection, though different expression levels of NKp46 and NKG2D were associated with different grades of fibrosis. In contrast to the liver, chronic HCV infection associated with an enrichment of CD161lowperforinhigh NK cells in the blood correlated with increased AST and 2B4 expression. However, the association of relatively discrete changes in the NK cell phenotype in the liver with the fibrosis stage nevertheless suggests an important role for the NK response. Overall these data suggest that tissue localization has a more pervasive effect on NK cells than the presence of chronic viral infection, during which these cells might be mostly attuned to limiting immunopathology. It will be important to characterize NK cells during early HCV infection, when they should have a critical role in limiting infection

Poorly cytotoxic terminally differentiated CD56(neg)CD16(pos) NK cells accumulate in Kenyan children with Burkitt lymphomas

Natural killer (NK) cells are critical for restricting viral infections and mediating tumor immunosurveillance. Epstein-Barr virus (EBV) and Plasmodium falciparum malaria are known risk factors for endemic Burkitt lymphoma (eBL), the most common childhood cancer in equatorial Africa. To date, the composition and function of NK cells have not been evaluated in eBL etiology or pathogenesis. Therefore, using multiparameter flow cytometry and in vitro killing assays, we compared NK cells from healthy children and children diagnosed with eBL in Kenya. We defined 5 subsets based on CD56 and CD16 expression, including CD56(neg)CD16(pos) We found that licensed and terminally differentiated perforin-expressing CD56(neg)CD16(pos) NK cells accumulated in eBL children, particularly in those with high EBV loads (45.2%) compared with healthy children without (6.07%) or with (13.5%) malaria exposure (P = .0007 and .002, respectively). This progressive shift in NK cell proportions was concomitant with fewer CD56(dim)CD16(pos) cells. Despite high MIP-1beta expression, CD56(neg)CD16(pos) NK cells had diminished cytotoxicity, with lower expression of activation markers NKp46, NKp30, and CD160 and the absence of TNF-alpha. Of note, the accumulation of poorly cytotoxic CD56(neg)CD16(pos) NK cells resolved in long-term eBL survivors. Our study demonstrates impaired NK cell-mediated immunosurveillance in eBL patients but with the potential to restore a protective NK cell repertoire after cancer treatment. Characterizing NK cell dysfunction during coinfections with malaria and EBV has important implications for designing immunotherapies to improve outcomes for children diagnosed with eBL

Low Levels of Peripheral CD161++CD8+ Mucosal Associated Invariant T (MAIT) Cells Are Found in HIV and HIV/TB Co-Infection

Background: High expression of CD161 on CD8+ T cells is associated with a population of cells thought to play a role in mucosal immunity. We wished to investigate this subset in an HIV and Mycobacterium tuberculosis (MTB) endemic African setting. Methods: A flow cytometric approach was used to assess the frequency and phenotype of CD161++CD8+ T cells. 80 individuals were recruited for cross-sectional analysis: controls (n = 18), latent MTB infection (LTBI) only (n = 16), pulmonary tuberculosis (TB) only (n = 8), HIV only (n = 13), HIV and LTBI co-infection (n = 15) and HIV and TB co-infection (n = 10). The impact of acute HIV infection was assessed in 5 individuals recruited within 3 weeks of infection. The frequency of CD161++CD8+ T cells was assessed prior to and during antiretroviral therapy (ART) in 14 HIV-positive patients. Results: CD161++CD8+ T cells expressed high levels of the HIV co-receptor CCR5, the tissue-homing marker CCR6, and the Mucosal-Associated Invariant T (MAIT) cell TCR Vα7.2. Acute and chronic HIV were associated with lower frequencies of CD161++CD8+ T cells, which did not correlate with CD4 count or HIV viral load. ART was not associated with an increase in CD161++CD8+ T cell frequency. There was a trend towards lower levels of CD161++CD8+ T cells in HIV-negative individuals with active and latent TB. In those co-infected with HIV and TB, CD161++CD8+ T cells were found at low levels similar to those seen in HIV mono-infection. Conclusions: The frequencies and phenotype of CD161++CD8+ T cells in this South African cohort are comparable to those published in European and US cohorts. Low-levels of this population were associated with acute and chronic HIV infection. Lower levels of the tissue-trophic CD161++ CD8+ T cell population may contribute to weakened mucosal immune defense, making HIV-infected subjects more susceptible to pulmonary and gastrointestinal infections and detrimentally impacting on host defense against TB

The Lantern Vol. 61, No. 1, December 1993

• In Order to Succeed • Essay • Power of Human Self-Interest: Man vs. Car • In Setterich • Wandering Wanda • Maybe Kitchens • Saltiness • Homecoming • Perfect • Sincerely, Jen • A Midterm and a Paper • Prophet Junkie • Soundless Memo • After Ireland, Part 1https://digitalcommons.ursinus.edu/lantern/1142/thumbnail.jp

The Lantern Vol. 62, No. 1, December 1994

• Hollow • A Little Knowledge is Dangerous • My Old Block • Life • The Natural Born Fool • Oracle • Formation of a Triangle • Marie on the Beach • The Tweed Derby • Tripping • In Vitro • The Character • Coming Home for Christmas • Unkempt • Too Much • Reimertanti-Ode • Seeds • Secrethttps://digitalcommons.ursinus.edu/lantern/1145/thumbnail.jp

Early and nonreversible decrease of CD161++ /MAIT cells in HIV infection

HIV infection is associated with immune dysfunction, perturbation of immune-cell subsets and opportunistic infections. CD161++ CD8+ T cells are a tissue-infiltrating population that produce IL17A, IL22, IFN, and TNFα, cytokines important in mucosal immunity. In adults they dominantly express the semi-invariant TCR Vα7.2, the canonical feature of mucosal associated invariant T (MAIT) cells and have been recently implicated in host defense against pathogens. We analyzed the frequency and function of CD161++ /MAIT cells in peripheral blood and tissue from patients with early stage or chronic-stage HIV infection. We show that the CD161++ /MAIT cell population is significantly decreased in early HIV infection and fails to recover despite otherwise successful treatment. We provide evidence that CD161++ /MAIT cells are not preferentially infected but may be depleted through diverse mechanisms including accumulation in tissues and activation-induced cell death. This loss may impact mucosal defense and could be important in susceptibility to specific opportunistic infections in HIV

The Lantern Vol. 61, No. 2, Summer 1994

• She Was a Woman of Dignity • Retake, Scene 16 • Las Vegas Sweatshirt • Pitcher Hill • In Preparation for Wisdom (Teeth) • Moist Slacks • My Mother\u27s Purse • It Comes and Goes Everyday • The Simplicity of Marriage • The First Performance • Hunger • Pushkin\u27s Dream • Tuesday, October 19 • Poetry of Baseball • Some Things are More Important Than Others • Musician • Of What Befell Our Good Knight • Piranha • Oceans Apart • Brooklyn Cantos • Snowshower • Thankfully in Australia • Toothpaste and Tuna Fish • Living Space • Blue Monday • Afterglow • A Path to Consider • Endless Summer • Scaredy-Cathttps://digitalcommons.ursinus.edu/lantern/1144/thumbnail.jp

Genome-wide association of multiple complex traits in outbred mice by ultra low-coverage sequencing

The authors wish to acknowledge excellent technical assistance from A. Kurioka, L. Swadling, C. de Lara, J. Ussher, R. Townsend, S. Lionikaite, A.S. Lionikiene, R. Wolswinkel and I. van der Made. We would like to thank T.M. Keane and A.G. Doran for their help in annotating variants and adding the FVB/NJ strain to the MGP. We thank the High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics and the Wellcome Trust Sanger Institute for the generation of the sequencing data. This work was funded by Wellcome Trust grant 090532/Z/09/Z (J.F.). Primary phenotyping of the mice was supported by the Mary Lyon Centre and Mammalian Genetics Unit (Medical Research Council, UK Hub grant G0900747 91070 and Medical Research Council, UK grant MC U142684172). D.A.B. acknowledges support from NIH R01AR056280. The sleep work was supported by the state of Vaud (Switzerland) and the Swiss National Science Foundation (SNF 14694 and 136201 to P.F.). The ECG work was supported by the Netherlands CardioVascular Research Initiative (Dutch Heart Foundation, Dutch Federation of University Medical Centres, Netherlands Organization for Health Research and Development and the Royal Netherlands Academy of Sciences) PREDICT project, InterUniversity Cardiology Institute of the Netherlands (ICIN; 061.02; C.A.R. and C.R.B.). N.C. is supported by the Agency of Science, Technology and Research (A*STAR) Graduate Academy. R.W.D. is supported by a grant from the Wellcome Trust (097308/Z/11/Z).Peer reviewedPostprin