Characterization of the Infant Immune System and the Influence and Immunogenicity of BCG Vaccination in Infant and Adult Rhesus Macaques

In many countries where tuberculosis (TB) is endemic, the Bacillus Calmette–Guérin (BCG) vaccine is given as close to birth as possible to protect infants and children from severe forms of TB. However, BCG has variable efficacy and is not as effective against adult pulmonary TB. At present, most animal models used to study novel TB vaccine candidates rely on the use of adult animals. Human studies show that the infant immune system is different to that of an adult. Understanding how the phenotypic profile and functional ability of the immature host immune system compares to that of a mature adult, together with the subsequent BCG immune response, is critical to ensuring that new TB vaccines are tested in the most appropriate models. BCG-specific immune responses were detected in macaques vaccinated within a week of birth from six weeks after immunization indicating that neonatal macaques are able to generate a functional cellular response to the vaccine. However, the responses measured were significantly lower than those typically observed following BCG vaccination in adult rhesus macaques and infant profiles were skewed towards the activation and attraction of macrophages and monocytes and the synthesis in addition to release of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-α. The frequency of specific immune cell populations changed significantly through the first three years of life as the infants developed into young adult macaques. Notably, the CD4:CD8 ratio significantly declined as the macaques aged due to a significant decrease in the proportion of CD4+ T-cells relative to a significant increase in CD8+ T-cells. Also, the frequency of both CD4+ and CD8+ T-cells expressing the memory marker CD95, and memory subset populations including effector memory, central memory and stem cell memory, increased significantly as animals matured. Infant macaques, vaccinated with BCG within a week of birth, possessed a significantly higher frequency of CD14+ classical monocytes and granulocytes which remained different throughout the first three years of life compared to unvaccinated age matched animals. These findings, along with the increase in monokines following vaccination in infants, may provide an insight into the mechanism by which vaccination with BCG is able to provide non-specific immunity against non-mycobacterial organisms.

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Prolonged activation of nasal immune cell populations and development of tissue-resident SARS-CoV-2 specific CD8 T cell responses following COVID-19

10.1101/2021.04.19.21255727 ◽

2021 ◽

Author(s):

Anna H.E. Roukens ◽

Marion König ◽

Tim Dalebout ◽

Tamar Tak ◽

Shohreh Azimi ◽

...

Keyword(s):

T Cells ◽

Immune System ◽

T Cell ◽

Nasal Mucosa ◽

Immune Cell ◽

Inflammatory Responses ◽

Upper Airway ◽

Effector Memory ◽

Long Term Effects ◽

Activated T Cells

AbstractThe immune system plays a major role in Coronavirus Disease 2019 (COVID-19) pathogenesis, viral clearance and protection against re-infection. Immune cell dynamics during COVID-19 have been extensively documented in peripheral blood, but remain elusive in the respiratory tract. We performed minimally-invasive nasal curettage and mass cytometry to characterize nasal immune cells of COVID-19 patients during and 5-6 weeks after hospitalization. Contrary to observations in blood, no general T cell depletion at the nasal mucosa could be detected. Instead, we observed increased numbers of nasal granulocytes, monocytes, CD11c+ NK cells and exhausted CD4+ T effector memory cells during acute COVID-19 compared to age-matched healthy controls. These pro-inflammatory responses were found associated with viral load, while neutrophils also negatively correlated with oxygen saturation levels. Cell numbers mostly normalized following convalescence, except for persisting CD127+ granulocytes and activated T cells, including CD38+ CD8+ tissue-resident memory T cells. Moreover, we identified SARS-CoV-2 specific CD8+ T cells in the nasal mucosa in convalescent patients. Thus, COVID-19 has both transient and long-term effects on the immune system in the upper airway.

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Immune System Deregulation Predicts Outcome in Diffuse Large B Cell Lymphoma (DLBCL)

Blood ◽

10.1182/blood-2020-143104 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 33-34

Author(s):

Edward Truelove ◽

Joseph G Taylor ◽

Andrew James Clear ◽

Mariarita Calaminici ◽

Professor John G. Gribben

Keyword(s):

T Cells ◽

Immune System ◽

T Cell ◽

Immune Cell ◽

Prognostic Score ◽

B Cell Lymphoma ◽

Cell Cluster ◽

Effector Memory ◽

Hla Dr ◽

Cytokine Levels

Background: Treatment failure after RCHOP is associated with poor outcome in DLBCL. Despite considerable immune system variation among individual patients, the diagnostic absolute monocyte (AMC) and absolute lymphocyte (ALC) counts can reproducibly separate DLBCL patients with different outcomes. In addition, polymorphisms in immune regulating cytokines are associated with NHL risk and cytokine deregulation can predict response to RCHOP. This suggests distinct patterns of immune system deregulation in DLBCL which may serve to guide prognosis and therapy. Aim: To investigate immune cell and cytokine deregulation in DLBCL. Methods: Diagnostic AMC and ALC from 116 DLBCL patients and 111 healthy stem cell donors were assessed. 20 cytokines were measured in duplicate in serum samples from 34 DLBCL patients with known outcome and 11 health donors using the mesoscale discovery (MSD) electrochemiluminescence platform. The 10 most deregulated cytokines were measured in duplicate in 30 additional DLBCL patients. Peripheral blood mononuclear cells (PBMCs) were analysed by mass cytometry (MC) from 33 of these patients with a myeloid focused panel (29 markers) and from 27 with a T cell directed panel (28 markers). A standard control healthy donor sample was acquired with each MC batch. The OMIQ platform was used for gating and high dimensional data analysis. Results: In DLBCL median AMC was higher (p<0.0001) and ALC lower (p=0.0036). The AMC and ALC prognostic score separated DLBCL into 3 groups with distinct outcomes (p<0.0001), independent of cell of origin (COO). 8/20 cytokines were significantly elevated in DLBCL (p<0.05). IL-1RA (p=0.025), IL-6 (p=0.0002), IL-10 (p=0.01), MIP-1a (p=0.003) and TNF (p=0.0056) were significantly more elevated in DLBCL patients who subsequently had relapse/refractory (R/R) disease within 12 months of RCHOP (n=15) compared to those with ongoing remission > 24 months (CR) (n=46). After MC acquisition and normalization, PBMC populations were assessed as a percentage of CD45+ events by outcome (n=33). CD14+ monocytes were higher and CD3+ T cells lower at diagnosis in DLBCL with R/R disease (p<0.05). CD4+ T cells, CD8+ T cells, CD19+ B cells, NK, NKT and DC were not significantly different. Unsupervised clustering with FlowSOM followed by differential abundance analysis using edgeR was performed to dissect the PBMC populations above into subpopulations. This identified 3 classical monocyte clusters and 1 CD8+ T cell cluster associated with R/R DLBCL (-log10 FDR >1.3). The classical monocyte clusters all expressed the myeloid markers CD11b, CD31, CD33, SIRPa (CD172a) and CCR2 (CD192), the Fc gamma receptors CD32 and CD64 and the activation marker CD38. 2 clusters expressed HLA-DR and CD206 and were differentiated by CD13+ (cluster09) or CD40/CD86+ (cluster23). The other cluster had a suppressor phenotype with low HLA-DR and expressed CD163 and CD184 (cluster12). The differentiating T cell cluster was a CD45RA-CCR7- CD8 effector memory population (Tem) with an EM3 phenotype (CD27-, CD28-) and T-bet, cytotoxic marker (granzyme, perforin) and PD-1 expression (cluster10). To identify co-deregulated immune cell / cytokine relationships in DLBCL contributing to R/R disease we used correlation analysis across PBMC populations, differentiating clusters and cytokine levels. CD14+ correlated positively with cluster9 (classical monocyte), cluster10 (Tem), IL-1RA, IL-6, and MIP-1a (p<0.05). CD3+ and CD4+, but not CD8+ correlated negatively with IL-1RA, IL-6 and MIP-1a (p<0.05). Cluster9 and cluster10 both correlated negatively with CD3+ and CD4+, but not with each other or cytokine levels. PBMC populations, differentiating clusters, and cytokine levels were not significantly different based on cell COO, except for IL-1RA which was elevated in non-GCB type (p=0.0148). Conclusion: We find deregulated immune cell and cytokine production in DLBCL, which is associated with R/R disease and largely independent of COO. Immune profiling with MC identified 3 distinct classical monocyte clusters and 1 CD8 Tem cluster associated with subsequent relapse. These differentiating clusters likely reflect immune dysfunction and contribute to the prognostic nature of the AMC / ALC. Further ongoing work is assessing which immune are cells secreting the most deregulated cytokines, with the aim of identifying biomarkers and targetable pathways. Disclosures No relevant conflicts of interest to declare.

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Antigen presentation by type 3 innate lymphoid cells instructs the differentiation of gut microbiota-specific regulatory T cells

10.1101/2021.11.19.469318 ◽

2021 ◽

Author(s):

Ranit Kedmi ◽

Tariq Najar ◽

Kailin R. Mesa ◽

Allyssa Grayson ◽

Lina Kroehling ◽

...

Keyword(s):

T Cells ◽

Immune System ◽

Cell Differentiation ◽

Antigen Presentation ◽

Th17 Cells ◽

Immune Cell ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Host Immune System ◽

Type 3

The mutualistic relationship of gut-resident microbiota and cells of the host immune system promotes homeostasis that ensures maintenance of the microbial community and of a poised, but largely non-aggressive, immune cell compartment1,2. Consequences of disturbing this balance, by environmental or genetic factors, include proximal inflammatory conditions, like Crohn's disease, and systemic illnesses, both metabolic and autoimmune. One of the means by which this equilibrium is achieved is through induction of both effector and suppressor or regulatory arms of the adaptive immune system. In mice, Helicobacter species induce regulatory (iTreg) and follicular helper (Tfh) T cells in the colon-draining mesenteric lymph nodes under homeostatic conditions, but can instead induce inflammatory Th17 cells and colitis when iTreg cells are compromised3,4. How Helicobacter hepaticus and other gut bacteria direct T cells to adopt distinct functions remains poorly understood. Here, we investigated which cells and molecular components are required to convey the microbial instruction for the iTreg differentiation program. We found that antigen presentation by cells expressing RORγt, rather than by classical dendritic cells, was both required and sufficient for iTreg induction. These RORγt+ cells, likely to be type 3 innate lymphoid cells (ILC3), require the MHC class II antigen presentation machinery, the chemokine receptor CCR7, and αv integrin, which activates TGF-β, for iTreg cell differentiation. In the absence of any of these, instead of iTreg cells there was expansion of microbiota-specific pathogenic Th17 cells, which were induced by other antigen presenting cells (APCs) that did not require CCR7. Thus, intestinal commensal microbes and their products target multiple APCs with pre-determined features suited to directing appropriate T cell differentiation programs, rather than a common APC that they endow with appropriate functions. Our results illustrate the ability of microbiota to exploit specialized functions of distinct innate immune system cells, targeting them to achieve the desired composition of equipoised T cells, thus maintaining tolerance.

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The Kv1.3 K+ channel in the immune system and its “precision pharmacology” using peptide toxins

Biologia Futura ◽

10.1007/s42977-021-00071-7 ◽

2021 ◽

Vol 72 (1) ◽

pp. 75-83

Author(s):

Zoltan Varga ◽

Gabor Tajti ◽

Gyorgy Panyi

Keyword(s):

T Cells ◽

Immune System ◽

Ion Channels ◽

Rational Drug Design ◽

Scorpion Toxin ◽

Effector Memory ◽

K Channel ◽

Effector Memory T Cells ◽

Human T Cells ◽

Rational Drug

AbstractSince the discovery of the Kv1.3 voltage-gated K+ channel in human T cells in 1984, ion channels are considered crucial elements of the signal transduction machinery in the immune system. Our knowledge about Kv1.3 and its inhibitors is outstanding, motivated by their potential application in autoimmune diseases mediated by Kv1.3 overexpressing effector memory T cells (e.g., Multiple Sclerosis). High affinity Kv1.3 inhibitors are either small organic molecules (e.g., Pap-1) or peptides isolated from venomous animals. To date, the highest affinity Kv1.3 inhibitors with the best Kv1.3 selectivity are the engineered analogues of the sea anemone peptide ShK (e.g., ShK-186), the engineered scorpion toxin HsTx1[R14A] and the natural scorpion toxin Vm24. These peptides inhibit Kv1.3 in picomolar concentrations and are several thousand-fold selective for Kv1.3 over other biologically critical ion channels. Despite the significant progress in the field of Kv1.3 molecular pharmacology several progressive questions remain to be elucidated and discussed here. These include the conjugation of the peptides to carriers to increase the residency time of the peptides in the circulation (e.g., PEGylation and engineering the peptides into antibodies), use of rational drug design to create novel peptide inhibitors and understanding the potential off-target effects of Kv1.3 inhibition.

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Of Mice, Dogs, Pigs, and Men: Choosing the Appropriate Model for Immuno-Oncology Research

ILAR Journal ◽

10.1093/ilar/ily014 ◽

2018 ◽

Vol 59 (3) ◽

pp. 247-262 ◽

Cited By ~ 11

Author(s):

Nana H Overgaard ◽

Timothy M Fan ◽

Kyle M Schachtschneider ◽

Daniel R Principe ◽

Lawrence B Schook ◽

...

Keyword(s):

Immune System ◽

Immune Cell ◽

Tumor Formation ◽

Genetically Engineered ◽

Model Systems ◽

High Rate ◽

Host Immune System ◽

Cancer Immunoediting ◽

Oncology Research ◽

Experimental Cancer

Abstract The immune system plays dual roles in response to cancer. The host immune system protects against tumor formation via immunosurveillance; however, recognition of the tumor by immune cells also induces sculpting mechanisms leading to a Darwinian selection of tumor cell variants with reduced immunogenicity. Cancer immunoediting is the concept used to describe the complex interplay between tumor cells and the immune system. This concept, commonly referred to as the three E’s, is encompassed by 3 distinct phases of elimination, equilibrium, and escape. Despite impressive results in the clinic, cancer immunotherapy still has room for improvement as many patients remain unresponsive to therapy. Moreover, many of the preclinical results obtained in the widely used mouse models of cancer are lost in translation to human patients. To improve the success rate of immuno-oncology research and preclinical testing of immune-based anticancer therapies, using alternative animal models more closely related to humans is a promising approach. Here, we describe 2 of the major alternative model systems: canine (spontaneous) and porcine (experimental) cancer models. Although dogs display a high rate of spontaneous tumor formation, an increased number of genetically modified porcine models exist. We suggest that the optimal immuno-oncology model may depend on the stage of cancer immunoediting in question. In particular, the spontaneous canine tumor models provide a unique platform for evaluating therapies aimed at the escape phase of cancer, while genetically engineered swine allow for elucidation of tumor-immune cell interactions especially during the phases of elimination and equilibrium.

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

PLoS ONE ◽

10.1371/journal.pone.0258743 ◽

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.

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Single-Cell Analysis of the Neonatal Immune System Across the Gestational Age Continuum

Frontiers in Immunology ◽

10.3389/fimmu.2021.714090 ◽

2021 ◽

Vol 12 ◽

Author(s):

Laura S. Peterson ◽

Julien Hedou ◽

Edward A. Ganio ◽

Ina A. Stelzer ◽

Dorien Feyaerts ◽

...

Keyword(s):

T Cells ◽

Immune System ◽

Single Cell ◽

Gestational Age ◽

Immune Cell ◽

Single Cell Analysis ◽

Inflammatory Diseases ◽

Interferon Α ◽

Cytotoxic Lymphocytes ◽

Neonatal Immune System

Although most causes of death and morbidity in premature infants are related to immune maladaptation, the premature immune system remains poorly understood. We provide a comprehensive single-cell depiction of the neonatal immune system at birth across the spectrum of viable gestational age (GA), ranging from 25 weeks to term. A mass cytometry immunoassay interrogated all major immune cell subsets, including signaling activity and responsiveness to stimulation. An elastic net model described the relationship between GA and immunome (R=0.85, p=8.75e-14), and unsupervised clustering highlighted previously unrecognized GA-dependent immune dynamics, including decreasing basal MAP-kinase/NFκB signaling in antigen presenting cells; increasing responsiveness of cytotoxic lymphocytes to interferon-α; and decreasing frequency of regulatory and invariant T cells, including NKT-like cells and CD8+CD161+ T cells. Knowledge gained from the analysis of the neonatal immune landscape across GA provides a mechanistic framework to understand the unique susceptibility of preterm infants to both hyper-inflammatory diseases and infections.

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Identification of human immune cell subtypes most responsive to IL-1β–induced inflammatory signaling using mass cytometry

Science Signaling ◽

10.1126/scisignal.abc5763 ◽

2021 ◽

Vol 14 (673) ◽

pp. eabc5763 ◽

Cited By ~ 1

Author(s):

Hema Kothari ◽

Corey M. Williams ◽

Chantel McSkimming ◽

Fabrizio Drago ◽

Melissa A. Marshall ◽

...

Keyword(s):

T Cells ◽

Transcription Factor ◽

Mononuclear Cells ◽

Immune Cell ◽

Human Peripheral Blood ◽

Effector Memory ◽

High Morbidity ◽

Cytokine Storm ◽

Mass Cytometry ◽

Myeloid Dendritic Cells

IL-1β is a key mediator of the cytokine storm linked to high morbidity and mortality from COVID-19, and IL-1β blockade with anakinra and canakinumab during COVID-19 infection has entered clinical trials. Using mass cytometry of human peripheral blood mononuclear cells, we identified effector memory CD4+ T cells and CD4−CD8low/−CD161+ T cells, specifically those positive for the chemokine receptor CCR6, as the circulating immune subtypes with the greatest response to IL-1β. This response manifested as increased phosphorylation and, thus, activation of the proinflammatory transcription factor NF-κB and was also seen in other subsets, including CD11c+ myeloid dendritic cells, classical monocytes, two subsets of natural killer cells (CD16−CD56brightCD161− and CD16−CD56dimCD161+), and lineage− (Lin−) cells expressing CD161 and CD25. IL-1β also induced a rapid but less robust increase in the phosphorylation of the kinase p38 as compared to that of NF-κB in most of these immune cell subsets. Prolonged IL-1β stimulation increased the phosphorylation of the transcription factor STAT3 and to a lesser extent that of STAT1 and STAT5 across various immune cell types. IL-1β–induced production of IL-6 likely led to the activation of STAT1 and STAT3 at later time points. Interindividual heterogeneity and inhibition of STAT activation by anakinra raise the possibility that assays measuring NF-κB phosphorylation in response to IL-1β in CCR6+ T cell subtypes could identify those patients at higher risk of cytokine storm and most likely to benefit from IL-1β–neutralizing therapies.

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

Clinical and Vaccine Immunology ◽

10.1128/cvi.00289-15 ◽

2015 ◽

Vol 22 (9) ◽

pp. 992-1003 ◽

Cited By ~ 26

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.

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Immune cell composition in normal human kidneys

Scientific Reports ◽

10.1038/s41598-020-72821-x ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Jun-Gyu Park ◽

Myeongsu Na ◽

Min-Gang Kim ◽

Su Hwan Park ◽

Hack June Lee ◽

...

Keyword(s):

T Cells ◽

Immune Cells ◽

Immune Cell ◽

Kidney Diseases ◽

Myeloid Cells ◽

Human Kidney ◽

Effector Memory ◽

Immune Cell Subsets ◽

Immunological Mechanisms ◽

Normal Human

Abstract An understanding of immunological mechanisms in kidney diseases has advanced using mouse kidneys. However, the profiling of immune cell subsets in human kidneys remains undetermined, particularly compared with mouse kidneys. Normal human kidneys were obtained from radically nephrectomised patients with urogenital malignancy (n = 15). Subsequently, human kidney immune cell subsets were analysed using multicolor flow cytometry and compared with subsets from C57BL/6 or BALB/c mice under specific pathogen-free conditions. Twenty kidney sections from healthy kidney donors or subjects without specific renal lesions were additionally analysed by immunohistochemistry. In human kidneys, 47% ± 12% (maximum 63%) of immune cells were CD3+ T cells. Kidney CD4+ and CD8+ T cells comprised 44% and 56% of total T cells. Of these, 47% ± 15% of T cells displayed an effector memory phenotype (CCR7− CD45RA− CD69−), and 48% ± 19% were kidney-resident cells (CCR7− CD45RA− CD69+). However, the proportions of human CD14+ and CD16+ myeloid cells were approximately 10% of total immune cells. A predominance of CD3+ T cells and a low proportion of CD14+ or CD68+ myeloid cells were also identified in healthy human kidney sections. In mouse kidneys, kidney-resident macrophages (CD11blow F4/80high) were the most predominant subset (up to 50%) but the proportion of CD3+ T cells was less than 20%. These results will be of use in studies in which mouse results are translated into human cases under homeostatic conditions or with disease.

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