scholarly journals BCG vaccination induces enhanced frequencies of memory T and B cells and dendritic cell subsets in elderly individuals

2020 ◽  
Author(s):  
Nathella Pavan Kumar ◽  
Chandrasekaran Padmapriyadarsini ◽  
Anuradha Rajamanickam ◽  
Perumal Kannabiran Bhavani ◽  
Arul Nancy ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cd8 T Cells ◽  
Effector Memory ◽  
Memory Cd8 T Cells ◽  
Elderly Individuals ◽  
Bcg Vaccination ◽  
Dendritic Cell Subsets ◽  
Antibody Levels ◽  
Memory Cd4 T Cells

AbstractBackgroundBCG vaccination is known to induce innate immune memory, which confers protection against heterologous infections. However, the effect of BCG vaccination on the conventional innate and adaptive immune cells subsets is not well characterized.MethodsWe investigated the impact of BCG vaccination on the frequencies of T cell, B cell, monocyte and dendritic cell subsets as well as total antibody levels in a group of healthy elderly individuals (age 60-80 years) at one month post vaccination as part of our clinical study to examine the effect of BCG on COVID-19.ResultsOur results demonstrate that BCG vaccination induced enhanced frequencies of central and effector memory CD4+ T cells and diminished frequencies of naïve, transitional memory, stem cell memory CD4+ T cells and regulatory T cells. In addition, BCG vaccination induced enhanced frequencies of central, effector and terminal effector memory CD8+ T cells and diminished frequencies of naïve, transitional memory and stem cell memory CD8+T cells. BCG vaccination also induced enhanced frequencies of immature, classical and activated memory B cells and plasma cells and diminished frequencies of naïve and atypical memory B cells. While BCG vaccination did not induce significant alterations in monocytes subsets, it induced increased frequencies of myeloid and plasmacytoid DCs. Finally, BCG vaccination resulted in elevated levels of all antibody isotypes.ConclusionsBCG vaccination was associated with enhanced innate and adaptive memory cell subsets, as well as total antibody levels in elderly individuals, suggesting its potential utility in SARS-Cov2 infection by enhancing heterologous immunity.

scholarly journals BCG vaccination induces enhanced frequencies of memory T cells and altered plasma levels of common γc cytokines in elderly individuals

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0258743
Author(s):  
Nathella Pavan Kumar ◽  
Chandrasekaran Padmapriyadarsini ◽  
Anuradha Rajamanickam ◽  
Perumal Kannabiran Bhavani ◽  
Arul Nancy ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Cd8 T Cells ◽  
Plasma Levels ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Elderly Individuals ◽  
Bcg Vaccination ◽  
Adaptive Immune

BCG vaccination is known to induce innate immune memory, which confers protection against heterologous infections. However, the effect of BCG vaccination on the conventional adaptive immune cells subsets is not well characterized. We investigated the impact of BCG vaccination on the frequencies of T cell subsets and common gamma c (γc) cytokines in a group of healthy elderly individuals (age 60–80 years) at one month post vaccination as part of our clinical study to examine the effect of BCG on COVID-19. Our results demonstrate that BCG vaccination induced enhanced frequencies of central (p<0.0001) and effector memory (p<0.0001) CD4+ T cells and diminished frequencies of naïve (p<0.0001), transitional memory (p<0.0001), stem cell memory (p = 0.0001) CD4+ T cells and regulatory T cells. In addition, BCG vaccination induced enhanced frequencies of central (p = 0.0008), effector (p<0.0001) and terminal effector memory (p<0.0001) CD8+ T cells and diminished frequencies of naïve (p<0.0001), transitional memory (p<0.0001) and stem cell memory (p = 0.0034) CD8+T cells. BCG vaccination also induced enhanced plasma levels of IL-7 (p<0.0001) and IL-15 (p = 0.0020) but diminished levels of IL-2 (p = 0.0033) and IL-21 (p = 0.0020). Thus, BCG vaccination was associated with enhanced memory T cell subsets as well as memory enhancing γc cytokines in elderly individuals, suggesting its ability to induce non-specific adaptive immune responses.

scholarly journals Increased memory phenotypes of CD4+ and CD8+ T cells in children with sickle cell anaemia in Tanzania

2017 ◽  
Vol 19 (2) ◽  
Author(s):  
Emmanuel Balandya ◽  
Teri Reynolds ◽  
Said Aboud ◽  
Stephen Obaro ◽  
Julie Makani
Keyword(s):  
T Cells ◽  
B Cells ◽  
Sickle Cell ◽  
Cd8 T Cells ◽  
Sickle Cell Anaemia ◽  
Sub Saharan Africa ◽  
Effector Memory ◽  
Absolute Increase ◽  
Memory Cd8 T Cells ◽  
Activation Status

Background: Infection is an important cause of morbidity in children with sickle cell anaemia (SCA). However, little is currently known regarding the spectrum of adaptive immune derangement in SCA, especially of populations in Sub-Saharan Africa. In this study, we investigated the phenotype and activation status of T and B lymphocytes among children with SCA in Tanzania.Methods: We compared 30 children with SCA aged 1–6 years in steady-state with 10 age-matched controls. We assessed white blood cell count, T and B lymphocyte phenotype and activation status using an automated haematology analyser and multiparameter Flow Cytometry.Results: In children with SCA, the absolute lymphocyte, monocyte and granulocyte counts were all increased. There was also an increase in proportion of central/transitional memory (42.4% vs. 33.3%, p = 0.0100), effector memory (7.8% vs. 5.4%, p = 0.0086) and terminally differentiated (2.3% vs. 1.3%, p = 0.0355) CD4+ T cells as well as effector memory CD8+ T cells (21.3% vs. 11.5%, p = 0.0060) in children with SCA. In contrast, there was no difference in naïve, classical memory, atypical memory and IgM memory B-cells between the two groups. The level of activation of both T and B cells were comparable between children with and without SCA. Furthermore, we observed a significant inverse correlation between frequency of the effector memory CD8+ T cells and haematocrit (Spearman rho = -0.3859, p = 0.0352). Conclusions: Children with SCA in Tanzania show an absolute increase in all leukocyte types, including lymphocytes, with skewing of both CD4+ and CD8+ T cells towards the memory phenotypes. These findings provide insights on the development of adaptive immunity which may have implications on vaccine responsiveness, allo-immunisation, auto-immune diseases and transplant immunology in children with SCA.

Liquid biopsy of the immune environment: Evaluation of peripheral blood mononuclear cells (PBMCs) with CyTOF and response to trastuzumab (T)-based neoadjuvant chemotherapy (NAC) in HER2+ breast cancer (BC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 592-592
Author(s):  
Roberto Antonio Leon-Ferre ◽  
Kaitlyn McGrath ◽  
Vera J. Suman ◽  
Jodi M Carter ◽  
Krishna R. Kalari ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Clinical Characteristics ◽  
Immune Cell ◽  
Effector Memory ◽  
Memory Cd8 T Cells ◽  
Immune Cell Subsets

592 Background: Immune responses in the tumor microenvironment have prognostic and predictive value in BC. However, the potential of immune responses observed in peripheral blood as biomarkers in BC remains unclear. We have shown that a higher frequency of circulating monocytes and a lower frequency of antigen-experienced memory CD8+ T cells are associated with response to NAC in triple negative BC (Leon-Ferre et al SABCS 2019). Here, we used cytometry by time-of-flight (CyTOF) to evaluate associations between circulating immune cells, clinical features and response to T-based NAC in HER2+ BC. Methods: PBMC suspensions from 36 pts with stage I-III HER2+ BC were prospectively collected prior to initiation of T-based NAC, stained with 29 metal-tagged antibodies optimized to identify major human immune cell subsets, and acquired in the Helios CyTOF instrument. Differential abundance analysis of immune cells by clinical characteristics and by NAC response was evaluated using Wilcoxon rank sum test. % of immune cell subsets is presented as % of all PBMCs. Results: Most pts presented with ER- tumors (56%), measuring > 5cm (64%) and with nodal metastases (78%). After NAC, 16 pts (44%) achieved pathologic complete response (pCR). Analysis of preNAC PBMCs demonstrated a significantly higher number of B cells (8% vs 5%, p = 0.05) and effector memory CD8+ T cells (CD45RA-/CCR7-, 3 vs 1%, p = 0.02) in pts with pCR compared to those with residual disease. Of the B cell subsets, naïve B cells (CD24-/CD27-) were higher in pts who achieved pCR vs not (7% vs 4%, 0 = 0.04). Regarding clinical characteristics, cN+ pts at presentation exhibited a lower number of peripheral blood T cells compared to cN- pts (47% vs 63%, p = 0.03). Of the T cell subsets, overall CD4+ and naïve CD4+ T cells (CD45RA+/CCR7+) were lower in cN+ vs cN- pts (31% vs 45%, p = 0.05; and 11% vs 24%, p = 0.04). We also observed differences in CD56+/CD16- NK cells by ER status (ER- 1% vs ER+ 3%, p = 0.01), and a moderate negative correlation between age and % circulating CD8+ T cells (rho -0.4669, p = 0.004). Conclusions: Distinct peripheral blood immune cell profiles are observed in HER2+ BC at diagnosis, and are associated with response to T-based NAC and initial clinical characteristics. Notably, pts who later achieved pCR had a relative abundance of B cells and effector memory CD8+ T cells at diagnosis. These data suggest that immune cell phenotyping in peripheral blood may have potential as a biomarker to predict response to NAC in BC.

Potential role of host effector memory CD8+ T cells in marrow rejection after mixed chimerism induction in cynomolgus monkeys

2010 ◽  
Vol 23 (4) ◽  
pp. 194-203 ◽  
Author(s):  
Kiyoshi Setoguchi ◽  
Hidehiro Kishimoto ◽  
Sakiko Kobayashi ◽  
Hiroaki Shimmura ◽  
Hideki Ishida ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Potential Role ◽  
Mixed Chimerism ◽  
Effector Memory ◽  
Memory Cd8 T Cells ◽  
Cynomolgus Monkeys

scholarly journals Specific niches for lung-resident memory CD8+ T cells at the site of tissue regeneration enable CD69-independent maintenance

2016 ◽  
Vol 213 (13) ◽  
pp. 3057-3073 ◽  
Author(s):  
Shiki Takamura ◽  
Hideki Yagi ◽  
Yoshiyuki Hakata ◽  
Chihiro Motozono ◽  
Sean R. McMaster ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
De Novo ◽  
Memory T Cells ◽  
Tissue Injury ◽  
Effector Memory ◽  
Respiratory Pathogens ◽  
Damage Site ◽  
Memory Cd8 T Cells ◽  
Specific Localization

CD8+ tissue-resident memory T cells (TRM cells) reside permanently in nonlymphoid tissues and provide a first line of protection against invading pathogens. However, the precise localization of CD8+ TRM cells in the lung, which physiologically consists of a markedly scant interstitium compared with other mucosa, remains unclear. In this study, we show that lung CD8+ TRM cells localize predominantly in specific niches created at the site of regeneration after tissue injury, whereas peripheral tissue-circulating CD8+ effector memory T cells (TEM cells) are widely but sparsely distributed in unaffected areas. Although CD69 inhibited sphingosine 1–phosphate receptor 1–mediated egress of CD8+ T cells immediately after their recruitment into lung tissues, such inhibition was not required for the retention of cells in the TRM niches. Furthermore, despite rigid segregation of TEM cells from the TRM niche, prime-pull strategy with cognate antigen enabled the conversion from TEM cells to TRM cells by creating de novo TRM niches. Such damage site–specific localization of CD8+ TRM cells may be important for efficient protection against secondary infections by respiratory pathogens.

scholarly journals Evaluation of the Immunogenicity of Mycobacterium bovis BCG Delivered by Aerosol to the Lungs of Macaques

2015 ◽  
Vol 22 (9) ◽  
pp. 992-1003 ◽  
Author(s):  
A. D. White ◽  
C. Sarfas ◽  
K. West ◽  
L. S. Sibley ◽  
A. S. Wareham ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Mycobacterium Bovis ◽  
Cd8 T Cells ◽  
Bcg Vaccine ◽  
Effector Memory ◽  
Dependent Manner ◽  
Aerosol Delivery ◽  
Memory Phenotype ◽  
Bcg Vaccination

ABSTRACTNine million cases of tuberculosis (TB) were reported in 2013, with a further 1.5 million deaths attributed to the disease. When delivered as an intradermal (i.d.) injection, theMycobacterium bovisBCG vaccine provides limited protection, whereas aerosol delivery has been shown to enhance efficacy in experimental models. In this study, we used the rhesus macaque model to characterize the mucosal and systemic immune response induced by aerosol-delivered BCG vaccine. Aerosol delivery of BCG induced both Th1 and Th17 cytokine responses. Polyfunctional CD4 T cells were detected in bronchoalveolar lavage (BAL) fluid and peripheral blood mononuclear cells (PBMCs) 8 weeks following vaccination in a dose-dependent manner. A similar trend was seen in peripheral gamma interferon (IFN-γ) spot-forming units measured by enzyme-linked immunosorbent spot (ELISpot) assay and serum anti-purified protein derivative (PPD) IgG levels. CD8 T cells predominantly expressed cytokines individually, with pronounced tumor necrosis factor alpha (TNF-α) production by BAL fluid cells. T-cell memory phenotype analysis revealed that CD4 and CD8 populations isolated from BAL fluid samples were polarized toward an effector memory phenotype, whereas the frequencies of peripheral central memory T cells increased significantly and remained elevated following aerosol vaccination. Expression patterns of the α4β1 integrin lung homing markers remained consistently high on CD4 and CD8 T cells isolated from BAL fluid and varied on peripheral T cells. This characterization of aerosol BCG vaccination highlights features of the resulting mycobacterium-specific immune response that may contribute to the enhanced protection previously reported in aerosol BCG vaccination studies and will inform future studies involving vaccines delivered to the mucosal surfaces of the lung.

Sign in / Sign up

Export Citation Format

Share Document