scholarly journals 193 The Achilles VELOSTM Process 2 boosts the dose of highly functional clonal neoantigen-reactive T cells for precision personalized cell therapies

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A205-A205
Author(s):  
Eleni Kotsiou ◽  
Joe Robinson ◽  
Amber Rogers ◽  
Daisy Melandri ◽  
Amy Baker ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Manufacturing Process ◽  
Intracellular Cytokine Staining ◽  
Flow Cytometric Analysis ◽  
Effector Memory ◽  
Potency Assay ◽  
Link Type ◽  
Median Process ◽  
Specific Expansion

BackgroundAdoptive transfer of ex-vivo expanded tumor-infiltrating lymphocytes (TIL) has shown promise in the clinic. However, the non-specific expansion of TIL and the lack of understanding of the active component of TIL has resulted in poor correlation between clinical response and dose as well as poor understanding of response and resistance mechanisms. The VELOSTM manufacturing process generates a precision and personalized treatment modality by targeting clonal neoantigens with the incorporation of an antigen-specific expansion step to enrich the product for these specificities. Achilles has developed a second generation manufacturing process (VELOSTM Process 2) to boost the neoantigen-reactive cell dose while maintaining key qualitative features associated with function. Here we report the in-depth characterization of clonal neoantigen-reactive T cells (cNeT) products expanded using the two VELOSTM processes.MethodsMatched tumors and peripheral blood from patients undergoing routine surgery were obtained from patients with primary NSCLC or metastatic melanoma (NCT03517917). TIL were expanded from tumor fragments and peptide pools corresponding to the clonal mutations identified using the PELEUSTM bioinformatics platform were synthesized. cNeT were expanded by co-culture of TIL with peptide-pulsed autologous dendritic cells, with an optimized cytokine cocktail and co-stimulation for Process 2. Neoantigen reactivity was assessed using our proprietary potency assay with peptide pool re-challenge followed by intracellular cytokine staining. Single peptide reactivities were identified using ELISPOT and flow cytometric analysis for in-depth phenotyping of cNeT was performed.ResultsCD3+ T cells displayed higher fold expansion in Process 2 (median 77.4) compared to Process 1 (median 3.8)(n=5). Both processes showed similar CD3+ T cell content (median Process 1=91.3%, Process 2=96.9% n=5) and contained both CD4+ and CD8+ T cells showing reactivity to clonal neoantigens. Proportion of cells responding to neoantigen re-challenge was similar across both processes (median Process 1=19.9% and Process 2=18.2%) leading to higher reactive dose when coupled with higher T cell doses in Process 2. Phenotypically T cells were predominantly effector memory for both processes and Process 2 had lower frequencies of terminally differentiated T cells.ConclusionsAchilles’ proprietary potency assay enables the optimization of new processes that deliver high cNeT doses to patients by detecting the active drug component. We have generated proof of concept data that supports the transfer of the VELOSTM Process 2 to clinical manufacture for two first-in-human studies for the treatment of solid cancers.Ethics ApprovalThe samples for the study were collected under an ethically approved protocol (NCT03517917)

scholarly journals Detection of IFNγ-Secreting CD4+ and CD8+ Memory T Cells in COVID-19 Convalescents after Stimulation of Peripheral Blood Mononuclear Cells with Live SARS-CoV-2

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1490
Author(s):  
Victoria Matyushenko ◽  
Irina Isakova-Sivak ◽  
Igor Kudryavtsev ◽  
Arina Goshina ◽  
Anna Chistyakova ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Memory T Cells ◽  
Natural Infection ◽  
Intracellular Cytokine Staining ◽  
T Cell Responses ◽  
Effector Memory ◽  
Memory T Cell ◽  
Cell Responses ◽  
Stimulation Of

Background: New coronavirus SARS-CoV-2, a causative agent of the COVID-19 pandemic, has been circulating among humans since November 2019. Multiple studies have assessed the qualitative and quantitative characteristics of virus-specific immunity in COVID-19 convalescents, however, some aspects of the development of memory T-cell responses after natural SARS-CoV-2 infection remain uncovered. Methods: In most of published studies T-cell immunity to the new coronavirus is assessed using peptides corresponding to SARS-CoV-1 or SARS-CoV-2 T-cell epitopes, or with peptide pools covering various parts of the viral proteins. Here, we determined the level of CD4+ and CD8+ memory T-cell responses in COVID-19 convalescents by stimulating PBMCs collected 1 to 6 months after recovery with sucrose gradient-purified live SARS-CoV-2. IFNγ production by the central and effector memory helper and cytotoxic T cells was assessed by intracellular cytokine staining assay and flow cytometry. Results: Stimulation of PBMCs with live SARS-CoV-2 revealed IFNγ-producing T-helper effector memory cells with CD4+CD45RA−CCR7− phenotype, which persisted in circulation for up to 6 month after COVID-19. In contrast, SARS-CoV-2-specific IFNγ-secreting cytotoxic effector memory T cells were found at significant levels only shortly after the disease, but rapidly decreased over time. Conclusion: The stimulation of immune cells with live SARS-CoV-2 revealed a rapid decline in the pool of effector memory CD8+, but not CD4+, T cells after recovery from COVID-19. These data provide additional information on the development and persistence of cellular immune responses after natural infection, and can inform further development of T cell-based SARS-CoV-2 vaccines.

Virus-Specific T Lymphocytes Maintain Their In Vivo Phenotype and Functional Competence After Automated Processing To Generate a Cellular Product For Immunotherapy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3268-3268 ◽  
Author(s):  
Anne Richter ◽  
Liane Preussner ◽  
Verena Traska ◽  
Michaela Peters ◽  
Ayse Oysal ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Manufacturing Process ◽  
Ex Vivo ◽  
Selection Process ◽  
Effector Memory ◽  
Automated Manufacturing ◽  
Cell Processing ◽  
Secretion Assay

Abstract Introduction Adoptive transfer of virus-specific T cells is an encouraging strategy to manage severe and fatal infections in immunocompromised patients. To generalize this approach, a cGMP- compliant enrichment process of both CD4+ and CD8+ viral-specific T cells is necessary. Here, we used a newly established automated manufacturing process for rapid and efficient ex vivo selection of multi-virus-specific CD4+ and CD8+ T cells. We show how the isolated virus-specific T cells retain their original effector/memory status and their effector functions. Method Leukapheresis from healthy donors were used as starting material. Multi-virus or cytomegalovirus pp65 peptide-specific T cell products were generated in a novel closed cell-processing device with a fully automated manufacturing procedure. During this process white blood cells were stimulated with either a combination of peptide pools covering cytomegalovirus pp65, Epstein-Barr-Virus EBNA-1, BZLF1, and LMP2, and adenovirus hexon protein (n=6) or with a single pp65 peptide for four hours (n=4). Subsequently, virus-specific CD4+ and CD8+ T cells were magnetically enriched using the IFN-g secretion assay technology. In parallel, the reversible MHC/peptide multimer technology, which is restricted to CD8+ peptide-specific T cell enrichment, was used for comparison in a manual magnetic selection procedure for pp65 peptide-specific CD8+ T cells (n=4). All virus-specific T cell products were rested in vitro in the presence of T-cell-depleted PBMCs without addition of cytokines or antigens for up to 4 days. Expression of CD45RA, CCR7, CD28, CD69, CD137 as well as IFN-g production with and without cognate antigen(s)-restimulation were analyzed by flow cytometry before and up to 4 days after the selection process. Results Manufacturing of multi-virus and pp65 peptide-specific T cells using the IFN-g secretion assay technology requires a short period of antigen stimulation and IFN-g expression, therefore, up to 96% of T cells produced IFN-g in the enriched fraction. However, after a few days resting phase in culture, IFN-g production decreased drastically. In addition, we detected an upregulation of CD69 and CD137 in the IFN-g enriched T cell products directly and 24 hours after the selection process, respectively. The transient nature of activation could again be confirmed, as both, CD69 and CD137 were downregulated during the resting phase. Results were compared to pp65-peptide specific CD8+ T cell products generated by the MHC/peptide multimer technology, which does not require an antigen incubation step. Activation was also seen for these enriched T cells, even when the MHC/peptide complexes were released, while unprocessed and cultured PBMC did not show IFN-g secretion or activation marker expression; indicating that cell processing and not the culture conditions triggered the activation. To test the functionality of the generated T cell products, we re-incubated three days resting cells with the corresponding antigens. In all samples, independent of the technology used for selection, induction of IFN-g expression in up to 100% of T cells was observed. Thus, T cells in all the products were able to maintain their in vivo imprinted physiological role, i.e. IFN-g production after antigen contact. Furthermore we examined if cell processing influences the effector/memory status of virus-specific T cells. Because the MHC/peptide multimer technology is restricted to the selection of single peptide-specific CD8+ T cells only, we monitored CD45RA, CD28 and CCR7 expression on pp65-peptide specific CD8+ T cells either identified by IFN-g secretion or by MHC/peptide multimer staining before and directly after the enrichment. The frequency of CD45RA+ and CD28+ cell populations varied between the donors and CCR7 was not detected at all, but importantly the enrichment process did not induce phenotypic changes. This result demonstrates the phenotype is stable during the manufacturing process. Conclusion A newly developed automated manufacturing process for direct ex vivo enrichment of multi-virus-specific CD4+ and CD8+ T cell populations via the IFN-g secretion assay technology provides a product for immunotherapy, where the original phenotypic and functional characteristics of the cells are conserved. Hence this cellular product is expected to fight efficiently against viral infections upon adoptive transfer. Disclosures: Richter: Miltenyi Biotec GmbH: Employment. Preussner:Miltenyi Biotec: Employment. Traska:Miltenyi Biotec: Employment. Peters:Miltenyi Biotec: Employment. Oysal:Miltenyi Biotec: Employment. Ruhnke:Miltenyi Biotec: Employment. Brauns:Miltenyi Biotec: Employment. Kramer:Miltenyi Biotec: Employment. Schmitz:Miltenyi Biotec: Employment. Assenmacher:Miltenyi Biotec: Employment.

scholarly journals Persistent memory CD4+ and CD8+ T-cell responses in recovered severe acute respiratory syndrome (SARS) patients to SARS coronavirus M antigen

2007 ◽  
Vol 88 (10) ◽  
pp. 2740-2748 ◽  
Author(s):  
Litao Yang ◽  
Hui Peng ◽  
Zhaoling Zhu ◽  
Gang Li ◽  
Zitong Huang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Severe Acute Respiratory Syndrome ◽  
Flow Cytometric Analysis ◽  
Memory Cell ◽  
T Cell Response ◽  
M Protein ◽  
Effector Memory ◽  
Cell Phenotype ◽  
Human T Cell

The membrane (M) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is a major glycoprotein with multiple biological functions. In this study, we found that memory T cells against M protein were persistent in recovered SARS patients by detecting gamma interferon (IFN-γ) production using ELISA and ELISpot assays. Flow cytometric analysis showed that both CD4+ and CD8+ T cells were involved in cellular responses to SARS-CoV M antigen. Furthermore, memory CD8+ T cells displayed an effector memory cell phenotype expressing CD45RO− CCR7− CD62L−. In contrast, the majority of IFN-γ + CD4+ T cells were central memory cells with the expression of CD45RO+ CCR7+ CD62L−. The epitope screening from 30 synthetic overlapping peptides that cover the entire SARS-CoV M protein identified four human T-cell immunodominant peptides, p21-44, p65-91, p117-140 and p200-220. All four immunodominant peptides could elicit cellular immunity with a predominance of CD8+ T-cell response. This data may have important implication for developing SARS vaccines.

scholarly journals Immunization of Volunteers with Salmonella enterica Serovar Typhi Strain Ty21a Elicits the Oligoclonal Expansion of CD8+ T Cells with Predominant Vβ Repertoires

2005 ◽  
Vol 73 (6) ◽  
pp. 3521-3530 ◽  
Author(s):  
Rosângela Salerno-Gonçalves ◽  
Rezwanul Wahid ◽  
Marcelo B. Sztein
Keyword(s):  
T Cells ◽  
T Cell ◽  
Salmonella Enterica ◽  
Flow Cytometric Analysis ◽  
Cell Receptor ◽  
Effector Memory ◽  
Color Flow ◽  
Cell Clones ◽  
Effector Memory Cells ◽  
Ifn Γ

ABSTRACT CD8+ T cells are likely to play an important role in host defense against Salmonella enterica serovar Typhi by several effector mechanisms, including lysis of infected cells (cytotoxicity) and gamma interferon (IFN-γ) secretion. In an effort to better understand these responses, we studied the T-cell receptor (TCR) repertoire of serovar Typhi-specific CD8+ T cells in humans. To this end, we determined the TCR beta chain (Vβ) usage of CD8+ T cells from three volunteers orally immunized with Ty21a typhoid vaccine by flow cytometry using a panel of monoclonal antibodies. Although TCR Vβ usage varied among volunteers, we identified oligoclonal Vβ subset expansions in individual volunteers (Vβ 2, 5.1, 8, 17, and 22 in volunteer 1; Vβ 1, 2, 5.1, 14, 17, and 22 in volunteer 2; and Vβ 3, 8, 14, and 16 in volunteer 3). These subsets were antigen specific, as shown by cytotoxicity and IFN-γ secretion assays on Vβ sorted cells and on T-cell clones derived from these volunteers. Moreover, eight-color flow cytometric analysis showed that these clones exhibited a T effector memory phenotype (i.e., CCR7− CD27− CD45RO+ CD62L−) and coexpressed gut homing molecules (e.g., high levels of integrin α4β7, intermediate levels of CCR9, and low levels of CD103). In conclusion, our results show that long-term T-cell responses to serovar Typhi in Ty21a vaccinees are oligoclonal, involving multiple TCR Vβ families. Moreover, these serovar Typhi-specific CD8+ T cells bearing defined Vβ specificities are phenotypically and functionally consistent with T effector memory cells with preferential gut homing potential.

scholarly journals Distinct Immune Signatures Indicative of Treatment Response and Immune-Related Adverse Events in Melanoma Patients under Immune Checkpoint Inhibitor Therapy

2021 ◽  
Vol 22 (15) ◽  
pp. 8017
Author(s):  
Robin Reschke ◽  
Philipp Gussek ◽  
Andreas Boldt ◽  
Ulrich Sack ◽  
Ulrike Köhl ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Adverse Events ◽  
Treatment Response ◽  
Immune Checkpoint ◽  
Mononuclear Cells ◽  
Flow Cytometric Analysis ◽  
Immune Monitoring ◽  
Effector Memory ◽  
Melanoma Patients

To identify potential early biomarkers of treatment response and immune-related adverse events (irAE), a pilot immune monitoring study was performed in stage IV melanoma patients by flow cytometric analysis of peripheral blood mononuclear cells (PBMC). Overall, 17 patients were treated with either nivolumab or pembrolizumab alone, or with a combination of nivolumab and ipilimumab every three weeks. Of 15 patients for which complete response assessment was available, treatment responders (n = 10) as compared to non-responders (n = 5) were characterized by enhanced PD-1 expression on CD8+ T cells immediately before treatment (median ± median absolute deviation/MAD 26.7 ± 10.4% vs. 17.2 ± 5.3%). Responders showed a higher T cell responsiveness after T cell receptor ex vivo stimulation as determined by measurement of programmed cell death 1 (PD-1) expression on CD3+ T cells before the second cycle of treatment. The percentage of CD8+ effector memory (CD8+CD45RA−CD45RO+CCR7−) T cells was higher in responders compared to non-responders before and immediately after the first cycle of treatment (median ± MAD 39.2 ± 7.3% vs. 30.5 ± 4.1% and 37.7 ± 4.6 vs. 24.0 ± 6.4). Immune-related adverse events (irAE) were accompanied by a higher percentage of activated CD4+ (CD4+CD38+HLADR+) T cells before the second treatment cycle (median ± MAD 14.9 ± 3.9% vs. 5.3 ± 0.4%). In summary, PBMC immune monitoring of immune-checkpoint inhibition (ICI) treatment in melanoma appears to be a promising approach to identify early markers of treatment response and irAEs.

Abstract 150: A Population of ApoB-100 Peptide-specific CD8+ T cells Tracks Atherosclerosis in ApoE-/- Mice

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Paul C Dimayuga ◽  
Xiaoning Zhao ◽  
Kuang-Yuh Chyu ◽  
Juliana Yano ◽  
Wai Man Lio ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
High Fat Diet ◽  
Flow Cytometric Analysis ◽  
Cd8 T Cell ◽  
Effector Memory ◽  
High Fat ◽  
Aortic Sinus ◽  
Mhc I

Background: Growing evidence supports a potential role for CD8+ T cells in atherogenesis, yet CD8+T cell antigens relevant to the disease remain to be defined. The current study was undertaken to identify and characterize endogenous, apoB-100 antigen-specific CD8+ T cells in atherosclerosis using fluorescently tagged, synthetic soluble MHC-I/peptide complexes called Pentamers (Pent). Methods and Results: Self-reactive CD8+ T cells were tested for recall response to a 20-mer peptide derived from apoB-100 under investigation as a potential vaccine candidate. CD8+IFN-γ+ T cells in splenocytes of apoE-/- mice were significantly increased after 48 hours of peptide stimulation, which was enhanced by a 6-week high fat diet. We then tested the apoB-100 peptide for potential binding to mouse MHC-I alleles H2Db and H2Kb. Binding assays identified 13 sequential fragments of 8-mer lengths with potential H2Kb binding. Pents corresponding to the 13 peptide fragments were then synthesized and were screened for reactivity to apoB-100-specific CD8+ T cells from 13 week-old wild type and apoE-/- mice fed normal chow (NC). Flow cytometric analysis detected higher binding to CD8+ T cells from apoE-/- mice for 3 Pents. The first of the 3, called Pent 2, was then selected as prototype for further analysis. The OVA Pentamer SIINFEKL confirmed Pent 2 specificity. Pent 2+CD8+ T cells were significantly increased in 13 week-old apoE-/- mice fed a high fat diet (HC) for 6 weeks compared to NC fed mice (0.99±0.15% vs. 0.51±0.02%, respectively, N=5 each; P<0.05). Pent 2+CD8+ T cells correlated with plaque size of apoE-/- mice fed NC or HC for 6 weeks (R 2 =0.645, P=0.005, N=10) or for 15-22 weeks (R 2 =0.623, P=0.001, N=13). Pent 2 blocked CD8+ cytolytic activity against oxLDL-primed macrophages by 50% (N=6; P<0.05). There was a shift in the Pent 2+CD8+ Vβ repertoire after HC feeding for 6 weeks compared to NC, with significantly increased Pent 2+CD8+ Effector Memory cells (65.0±5.7% vs. 48.8±6.0%, respectively; P<0.01). Flow cytometry of digested aortic sinus plaques confirmed presence of Pent 2+CD8+ T cells in atherosclerotic plaques. Conclusion: Our study provides evidence of a self-reactive, apoB-100-specific CD8+ T cell population that tracks atherosclerotic disease in apoE-/- mice.

scholarly journals Effect of the sphingosine-1-phosphate receptor modulator ozanimod on leukocyte subtypes in relapsing MS

2020 ◽  
Vol 7 (5) ◽  
pp. e839
Author(s):  
Sarah Harris ◽  
Jonathan Q. Tran ◽  
Harry Southworth ◽  
Collin M. Spencer ◽  
Bruce A.C. Cree ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
T Cell ◽  
Natural Killer ◽  
Phase 1 ◽  
Cell Counting ◽  
Effector Memory ◽  
Link Type ◽  
Cell Counts ◽  
Dose Dependent

ObjectiveTo better understand ozanimod's mechanism of action (MOA), we conducted exploratory analyses from a phase 1 study to characterize ozanimod's effect on circulating leukocyte subsets in patients with relapsing multiple sclerosis.MethodsAn open-label pharmacodynamic study randomized patients to oral ozanimod hydrochloride (HCl) 0.5 (n = 13) or 1 mg/d (n = 11) for ∼12 weeks (including 7-day dose escalation). Circulating leukocyte subsets were quantified using flow cytometry (days 28, 56, and 85) and epigenetic cell counting (days 2, 5, 28, 56, and 85) and compared with baseline (day 1) using descriptive statistics.ResultsOzanimod caused dose-dependent reductions in absolute lymphocyte counts. Observed by both methodologies, circulating CD19+ B- and CD3+ T-cell counts were reduced by >50% with ozanimod HCl 0.5 mg and >75% with 1 mg at day 85. Based on flow cytometry, ozanimod HCl 1 mg showed greater decreases in CD4+ than CD8+ T cells, greater decreases in both CD4+ and CD8+ central memory vs effector memory T cells, and reductions in mean CD4+ and CD8+ naive T cells by ≥90% at day 85. In the flow cytometry analysis, changes in monocytes, natural killer, and natural killer T cells were minimal. Using epigenetic cell counting, greater reductions for Th17 than T regulatory cells were determined.ConclusionOzanimod induced dose-dependent reductions in circulating B- and T-cell counts and differential effects on naive and memory CD4+ and CD8+ T cells and CD19+ B cells. Data characterized with both a novel epigenetic cell-counting method and flow cytometry support ozanimod's MOA.Clinical trial registration:clinicaltrials.govNCT02797015.

scholarly journals Longitudinal Changes in Cd4+, Cd8+ T Cell Phenotype and Activation Marker Expression Following Antiretroviral Therapy Initiation among Patients with Cryptococcal Meningitis

2019 ◽  
Vol 5 (3) ◽  
pp. 63
Author(s):  
Alice Bayiyana ◽  
Samuel Okurut ◽  
Rose Nabatanzi ◽  
Godfrey Zziwa ◽  
David R. Boulware ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cell Surface ◽  
Cd8 T Cells ◽  
Cryptococcal Meningitis ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Effector Memory ◽  
Memory Subset

Despite improvement in the prognosis of HIV/AIDS (human immunodeficiency virus/acquired immune deficiency syndrome) patients on antiretroviral therapy (ART), cryptococcal meningitis (CM) still causes 10–15% mortality among HIV-infected patients. The immunological impact of ART on the CD4+ and CD8+ T cell repertoire during cryptococcal co-infection is unclear. We determined longitudinal phenotypic changes in T cell subsets among patients with CM after they initiated ART. We hypothesized that ART alters the clonotypic phenotype and structural composition of CD4+ and CD8+ T cells during CM co-infection. For this substudy, peripheral blood mononuclear cells (PBMC) were isolated at four time points from CM patients following ART initiation during the parent study (ClinicalTrials.gov number, NCT01075152). Phenotypic characterization of CD4+ and CD8+ T cells was done using T cell surface marker monoclonal antibodies by flow cytometry. There was variation in the expression of immunophenotypic markers defining central memory (CD27+CD45R0+), effector memory (CD45R0+CD27–), immune activation (CD38+ and Human Leucocyte Antigen DR (HLA-DR+), and exhaustion (Programmed cell death protein one (PD-1) in the CD4+ T cell subset. In comparison to the CD4+ T cell population, the CD8+ central memory subset declined gradually with minimal increase in the effector memory subset. Both CD4+ and CD8+ T cell immune exhaustion and activation markers remained elevated over 12 weeks. The relative surge and decline in the expression of T cell surface markers outlines a variation in the differentiation of CD4+ T cells during ART treatment during CM co-infection.

scholarly journals Traditional Thai Massage Promoted Immunity in the Elderly via Attenuation of Senescent CD4+ T Cell Subsets: A Randomized Crossover Study

2021 ◽  
Vol 18 (6) ◽  
pp. 3210
Author(s):  
Kanda Sornkayasit ◽  
Amonrat Jumnainsong ◽  
Wisitsak Phoksawat ◽  
Wichai Eungpinichpong ◽  
Chanvit Leelayuwat
Keyword(s):  
T Cells ◽  
T Cell ◽  
Crossover Study ◽  
Intracellular Cytokine Staining ◽  
The Elderly ◽  
Complementary Therapy ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
T Subsets ◽  
Randomized Crossover Study

The beneficial physiological effects of traditional Thai massage (TTM) have been previously documented. However, its effect on immune status, particularly in the elderly, has not been explored. This study aimed to investigate the effects of multiple rounds of TTM on senescent CD4+ T cell subsets in the elderly. The study recruited 12 volunteers (61–75 years), with senescent CD4+ T cell subsets, who received six weekly 1-h TTM sessions or rest, using a randomized controlled crossover study with a 30-day washout period. Flow cytometry analysis of surface markers and intracellular cytokine staining was performed. TTM could attenuate the senescent CD4+ T cell subsets, especially in CD4+28null NKG2D+ T cells (n = 12; p < 0.001). The participants were allocated into two groups (low < 2.75% or high ≥ 2.75%) depending on the number of CD4+28null NKG2D+ T cells. After receiving TTM over 6 sessions, the cell population of the high group had significantly decreased (p < 0.001), but the low group had no significant changes. In conclusion, multiple rounds of TTM may promote immunity through the attenuation of aberrant CD4+ T subsets. TTM may be provided as a complementary therapy to improve the immune system in elderly populations.

scholarly journals Upregulation of PD-1 expression on circulating CD8+ but not CD4+ T cells is associated with tuberculosis infection in health care workers

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Cui-lin Shi ◽  
Jian-ping Zhang ◽  
Ping Xu ◽  
Jin Li ◽  
Jie Shen ◽  
...  
Keyword(s):  
Health Care ◽  
T Cells ◽  
T Cell ◽  
Health Care Workers ◽  
Cd4 T Cells ◽  
Receptor Expression ◽  
Effector Memory ◽  
Care Workers ◽  
Latent Tb ◽  
Latent Tb Infection

Abstract Background Health care workers (HCWs) are at risk for occupationally acquired Mycobacterium tuberculosis infection and tuberculosis (TB) disease due to repeated exposure to workplace tubercle bacilli. To determine whether continual mycobacterial stimulation correlates with increased expression of inhibitory T cell receptors, here we compared PD-1 receptor expression on surfaces of circulating T cells between naïve (uninfected) HCWs and HCWs with latent TB infection (LTBI). Result Data collected from 133 medical workers who met study selection criteria were included in the final analysis. QuantiFERON-TB Gold In-​Tube (QFT-GIT) testing yielded positive results for 32 HCWs, for an overall LTBI rate of 24.1%. Multivariate analysis identified HCW length of service > 15 years as an independent risk factor for a positive QFT-GIT result. In addition, comparisons of blood T cell subgroup profiles between QFT- and QFT+ groups indicated QFT+ subjects possessed greater proportions of mature (TM), transitional memory (TTM) and effector memory (TEM) CD4+ T cell subgroups and lower proportions of naïve T cells (TN). Moreover, the QFT+ group percentage of CD8+ T cells with detectable surface PD-1 was significantly higher than the corresponding percentage for the QFT- group. Meanwhile, no statistical intergroup difference was observed in percentages of CD4+ T cells with detectible surface PD-1. Conclusions Our data demonstrated that upregulated PD-1 expression on circulating CD8+, but not CD4+ T cells, was associated with latent TB infection of HCWs. As compared to other hospitals, occupational TB infection risk in our hospital was substantially mitigated by implementation of multitiered infection control measures.

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