scholarly journals Dynamics of Macrophage, T and B Cell Infiltration Within Pulmonary Granulomas Induced by Mycobacterium tuberculosis in Two Non-Human Primate Models of Aerosol Infection

2022 ◽  
Vol 12 ◽  
Author(s):  
Laura Hunter ◽  
Suzie Hingley-Wilson ◽  
Graham R. Stewart ◽  
Sally A. Sharpe ◽  
Francisco Javier Salguero
Keyword(s):  
T Cells ◽  
B Cells ◽  
Post Infection ◽  
Giant Cells ◽  
Cellular Interactions ◽  
Multinucleated Giant Cells ◽  
Acid Fast Bacilli ◽  
Cynomolgus Macaques ◽  
Pulmonary Granulomas ◽  
Human Primate

Non-human primate models of Tuberculosis (TB) are one of the most commonly used within the experimental TB field because they closely mimic the whole spectrum of disease progression of human TB. However, the early cellular interactions of the pulmonary granuloma are still not well understood. The use of this model allows investigation into the early interactions of cells within pulmonary granulomas which cannot be undertaken in human samples. Pulmonary granulomas from rhesus and cynomolgus macaques from two timepoints post infection were categorised into categories 1 – 6 (early to late stage granulomas) and immunohistochemistry was used to identify CD68+ macrophages, CD3+ T cells and CD20+ B cells. Multinucleated giant cells and acid-fast bacilli were also quantified. At week four post infection, cynomolgus macaques were found to have more CD68+ cells than rhesus in all but category 1 granulomas. Cynomolgus also had a significantly higher percentage of CD20+ B cells in category 1 granulomas. At week twelve post infection, CD68+ cells were most abundant in category 4 and 5 granulomas in both species; however, there were no significant differences between them. CD3+ T cells and CD20+ B cells were significantly higher in the majority of granuloma categories in cynomolgus compared to rhesus. Multinucleated giant cells and acid-fast bacilli were most abundant in categories 5 and 6 at week 12 post challenge in both species. This study has identified the basic cellular composition and spatial distribution of immune cells within pulmonary granulomas in both rhesus and cynomolgus macaques over time. The data from this study will add to the knowledge already gained in this field and may inform future research on vaccines and therapeutics for TB.

scholarly journals COVID-19 convalescents exhibit deficient humoral and T cell responses to variant of concern Spike antigens at 12 month post-infection

2021 ◽  
Author(s):  
Pablo Garcia-Valtanen ◽  
Christopher Martin Hope ◽  
Makutiro Ghislain Masavuli ◽  
Arthur Eng Lip Yeow ◽  
Harikrishnan Balachandran ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Post Infection ◽  
T Cell Responses ◽  
Memory B Cells ◽  
Pseudotyped Virus ◽  
Cell Responses ◽  
Specific Memory ◽  
Cell Functionality

Background The duration and magnitude of SARS-CoV-2 immunity after infection, especially with regard to the emergence of new variants of concern (VoC), remains unclear. Here, immune memory to primary infection and immunity to VoC was assessed in mild-COVID-19 convalescents one year after infection and in the absence of viral re-exposure or COVID-19 vaccination. Methods Serum and PBMC were collected from mild-COVID-19 convalescents at ~6 and 12 months after a COVID-19 positive PCR (n=43) and from healthy SARS-CoV-2-seronegative controls (n=15-40). Serum titers of RBD and Spike-specific Ig were quantified by ELISA. Virus neutralisation was assessed against homologous, pseudotyped virus and homologous and VoC live viruses. Frequencies of Spike and RBD-specific memory B cells were quantified by flow cytometry. Magnitude of memory T cell responses was quantified and phenotyped by activation-induced marker assay, while T cell functionality was assessed by intracellular cytokine staining using peptides specific to homologous Spike virus antigen and four VoC Spike antigens. Findings At 12 months after mild-COVID-19, >90% of convalescents remained seropositive for RBD-IgG and 88.9% had circulating RBD-specific memory B cells. Despite this, only 51.2% convalescents had serum neutralising activity against homologous live-SARS-CoV-2 virus, which decreased to 44.2% when tested against live B.1.1.7, 4.6% against B.1.351, 11.6% against P.1 and 16.2%, against B.1.617.2 VoC. Spike and non-Spike-specific T cells were detected in >50% of convalescents with frequency values higher for Spike antigen (95% CI, 0.29-0.68% in CD4+ and 0.11-0.35% in CD8+ T cells), compared to non-Spike antigens. Despite the high prevalence and maintenance of Spike-specific T cells in Spike 'high-responder' convalescents at 12 months, T cell functionality, measured by cytokine expression after stimulation with Spike epitopes corresponding to VoC was severely affected. Interpretations SARS-CoV-2 immunity is retained in a significant proportion of mild COVID-19 convalescents 12 months post-infection in the absence of re-exposure to the virus. Despite this, changes in the amino acid sequence of the Spike antigen that are present in current VoC result in virus evasion of neutralising antibodies, as well as evasion of functional T cell responses.

Abstract 288: Distribution of Pathological Features and Inflammatory Cells in Patients With Giant Cell Myocarditis

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
LIU SHANGYU ◽  
Yao Yan
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Giant Cells ◽  
Ventricular Septum ◽  
Free Wall ◽  
Pathological Features ◽  
Multinucleated Giant Cells ◽  
Giant Cell Myocarditis ◽  
Cardiac Lesions ◽  
The Right

Background: Giant-cell myocarditis (GCM) is a rare disease with a poor prognosis. The typical pathological features of GCM include an infiltration of multinucleated giant cells accompanied by numerous inflammatory immune cells. However, the etiology and pathophysiology of GCM remain largely unclear. Methods: Eight patients with pathological diagnoses with GCM underwent heart transplantation at our center. Hematoxylin- eosin (H-E) and Masson’s tri-chrome staining were performed on biopsies of the free walls of the right and left ventricles and interventricular septa of the original hearts to determine the characteristic distribution of cardiac lesions and the composition of infiltrating immune cells. A multiplex immunohistochemistry and multispectral imaging analysis were applied to further classify the specific types of inflammatory immune cells. Results: Inflammation found in a descending frequency gradually from the epicardium to the endocardium in the free wall of the left ventricle, but concentrated on the surface of right ventricular septum. Typical inflammatory infiltration and pathological changes were observed in the right-sided ventricular septum samples from all 8 patients. Numerous inflammatory immune cells, particularly CD4 + T cells, were detected in the lesion, which surrounded the emerging multinucleated giant cells. CD8 + T cells and a small number of regulatory T cells were scattered in the periphery. Conclusions: In GCM, cardiac lesions appear to concentrate particularly beneath the epicardium of the left ventricular free wall and the right side of the ventricular septum. These findings provide a rationale for the diagnostic use of conventional endocardial biopsy. The findings further suggest that myocardial injury is mediated by a variety of lymphocytes, especially CD4 + T cells.

scholarly journals Inflammatory Cells in Tissues of Gout Patients and Their Correlations with Comorbidities

2013 ◽  
Vol 7 (1) ◽  
pp. 26-31 ◽  
Author(s):  
Syeling Lai ◽  
Xiaodong Zhou
Keyword(s):  
Diabetes Mellitus ◽  
T Cells ◽  
Uric Acid ◽  
B Cells ◽  
Uric Acid Level ◽  
Acid Level ◽  
Plasma Cells ◽  
Pathological Finding ◽  
Inflammatory Cells ◽  
Giant Cells

Background: The major pathological finding of gout is the deposition of monosodium urate monohydrate (MSU) crystals with inflammatory infiltrate in the tissue. There have been many reports of in vitro analysis of inflammatory mechanism and comorbidities in gout. However, the associations of immune response cells and comorbidities of gout have not been well documented. Our studies aimed to examine the immune cell types and quantity in gout tissues, and to define the association of individual cell type with comorbidities. Methods: Surgically resected or biopsied tissues from 48 patients diagnosed as gout were used for this study. Cell count was performed on Hemotoxylin and Eosin stained sections for macrophages, plasma cells, neutrophils and on immunostained slides for T and B lymphocytes. Results: Hyperlipidemia, hypertension and diabetes mellitus were seen in 70.8%, 87.5% and 37.5% of patients, respectively. There were 35.6% and 37.8% of patients who admitted history of smoking and alcohol intake, respectively. Mean serum uric acid level was 8.5 mg/dl. The average body mass index was 30.1 kg/m2. H&E stained tissue sections demonstrated the crystalline deposits rimmed by palisading multinucleated giant cells, macrophages, neutrophils, plasma cells, T and B cells. Significant correlations between the clinical features and tissue inflammatory cells were observed in hyperlipidemia with number of T cells (p = 0.0363), hypertension with number of T cells and B cells (p = 0.0138 and 0.0033, respectively), diabetes mellitus with macrophages (p = 0.0016), and uric acid level with giant cells (p = 0.0088). Conclusion: Comorbidity factors including hyperlipidemia, hypertension and diabetes are significantly associated with the inflammatory cells in the tissues.

scholarly journals An outbreak of avian tuberculosis in peafowl (Pavo cristatus) and pheasants (Phasianus colchicus) in a zoological aviary inTurkey 

2012 ◽  
Vol 50 (No. 10) ◽  
pp. 446-450 ◽  
Author(s):  
O. Kul ◽  
R. Tunca ◽  
R. Haziroglu ◽  
Diker KS ◽  
S. Karahan
Keyword(s):  
Mycobacterium Avium ◽  
Giant Cells ◽  
Mycobacterium Avium Subsp ◽  
Phasianus Colchicus ◽  
Multinucleated Giant Cells ◽  
Tissue Samples ◽  
Acid Fast Bacilli ◽  
Pavo Cristatus ◽  
Histopathologic Findings

Avian tuberculosis was diagnosed histopathologically and microbiologically in two pheasants (Phasianus colchicus) and two peafowl (Pavo cristatus) kept in the same aviary. The incidence of avian tuberculosis in the aviary was 6%. Non-mineralized caseogranulomas were present in the liver (3 cases), spleen (3 cases), intestine (2 cases), lung (2 cases), and cloaca (1 case). Granulomas in the lung were present only in peafowl. The presence of granulomas in the lung of both infected peafowl suggests that peafowl were exposed to the agent via the respiratory route rather than the alimentary route. Histopathologic findings were typical of avian tuberculosis, including acid fast bacilli and centrally located caseo-necrosis surrounded by epitheloid macrophages, lymphocytes, and multinucleated giant cells. Mycobacterium avium subsp. avium was isolated from tissue samples of all infected birds.

scholarly journals Subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques

2021 ◽  
Vol 17 (7) ◽  
pp. e1009668
Author(s):  
Takushi Nomura ◽  
Hiroyuki Yamamoto ◽  
Masako Nishizawa ◽  
Trang Thi Thu Hau ◽  
Shigeyoshi Harada ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Post Infection ◽  
Clinical Manifestations ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Viral Rna ◽  
Viral Control ◽  
Cell Responses ◽  
Cynomolgus Macaques

SARS-CoV-2 infection presents clinical manifestations ranging from asymptomatic to fatal respiratory failure. Despite the induction of functional SARS-CoV-2-specific CD8+ T-cell responses in convalescent individuals, the role of virus-specific CD8+ T-cell responses in the control of SARS-CoV-2 replication remains unknown. In the present study, we show that subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques. Eight macaques were intranasally inoculated with 105 or 106 TCID50 of SARS-CoV-2, and three of the eight macaques were treated with a monoclonal anti-CD8 antibody on days 5 and 7 post-infection. In these three macaques, CD8+ T cells were undetectable on day 7 and thereafter, while virus-specific CD8+ T-cell responses were induced in the remaining five untreated animals. Viral RNA was detected in nasopharyngeal swabs for 10–17 days post-infection in all macaques, and the kinetics of viral RNA levels in pharyngeal swabs and plasma neutralizing antibody titers were comparable between the anti-CD8 antibody treated and untreated animals. SARS-CoV-2 RNA was detected in the pharyngeal mucosa and/or retropharyngeal lymph node obtained at necropsy on day 21 in two of the untreated group but undetectable in all macaques treated with anti-CD8 antibody. CD8+ T-cell responses may contribute to viral control in SARS-CoV-2 infection, but our results indicate possible containment of subacute viral replication in the absence of CD8+ T cells, implying that CD8+ T-cell dysfunction may not solely lead to viral control failure.

scholarly journals Malignancy induced haemophagocytosis by erthroid cells and its transformation into a multinucleated giant cells – A unique clinical image

2021 ◽  
Vol 5 (1) ◽  
pp. 007-007
Keyword(s):  
T Cells ◽  
Giant Cells ◽  
Clinical Image ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Multinucleated Giant Cells

Haemophagocytosis is a dysregulated immune condition characterised by both inflammation and uncontrolled activation of macrophages and T-cells, which causes aberrant cytokine release, leading to cytokine storm [1] it can be primary or secondary, depending upon the etiology.

scholarly journals CELLULAR INTERACTIONS IN THE PROLIFERATIVE RESPONSE OF HUMAN T AND B LYMPHOCYTES TO PHYTOMITOGENS AND ALLOGENEIC LYMPHOCYTES

1974 ◽  
Vol 139 (6) ◽  
pp. 1553-1567 ◽  
Author(s):  
Hans-Peter Lohrmann ◽  
Ligita Novikovs ◽  
Robert G. Graw
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
T Cell Activation ◽  
Proliferative Response ◽  
Cell Activation ◽  
Human Peripheral Blood ◽  
Cellular Interactions ◽  
Allogeneic Lymphocytes

In vitro studies were performed to determine the proliferative responsiveness of human peripheral blood thymus-dependent (T) and thymus-independent (B) lymphocytes to phytomitogens and allogeneic lymphocytes. Recombination of T and B cells, with selective inhibition of proliferation of one of the two populations, was used to identify cellular interactions which may contribute to cell proliferation. The distinctive feature of human T lymphocytes to form rosettes with unsensitized sheep erythrocytes was utilized to separate human peripheral blood lymphocytes into highly purified resetting (T) and non-rosetting (B) cells. The proliferative response of these separated lymphocyte subpopulations to various stimulants was assessed from the uptake of tritiated thymidine into DNA. Phytohemagglutinin, concanavalin A, pokeweed mitogen, and allogeneic lymphocytes stimulated separated T cells, whereas no proliferation was observed with the T-cell-depleted B-cell population. This suggests that it is the human T cell which is activated directly by these stimulants. In the presence of T cells (proliferating or nonproliferating), B cells were capable of proliferation following stimulation with phytomitogens, but not in response to histocompatibility antigens. Thus, T-cell-mediated B-cell proliferation contributes to the overall lymphocyte response in phytomitogen-stimulated T + B cell mixtures, but not in human mixed leukocyte cultures. T-cell activation by allogeneic cells required the presence of monocytes; in contrast, the three tested phytomitogens stimulated T cells in the absence of monocytes. This indicates that direct interaction of mitogens with lymphocyte membrane receptors is sufficient to trigger T cells into proliferative response. However, monocytes considerably enhanced the proliferative response of T cells in a dose-dependent fashion; this monocyte-dependent mechanism of T-cell activation was predominant at lower concentrations of phytomitogens, and contributed relatively less at higher mitogen doses. Both, the direct, monocyte-independent, and the indirect, monocyte-dependent T-lymphocyte activation contribute to the total in vitro response of lymphocyte preparations to phytomitogens.

scholarly journals 78. Oral Norovirus Vaccination in Humans Induces Plasmablast B-Cell Expansion and Follicular T-Cell Activation Comparable to Natural Infection

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S2-S2 ◽  
Author(s):  
Roberto Mateo ◽  
Karen Lin ◽  
Nikita Kolhatkar ◽  
David Taylor ◽  
Shaily Garg ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Immune Responses ◽  
Post Infection ◽  
Natural Infection ◽  
Vaccine Dose ◽  
Oral Tablet ◽  
Post Immunization

Abstract Background Norovirus (NoV) is a common cause of acute gastroenteritis, but no vaccines are currently licensed. Vaxart is developing an oral tableted NoV vaccine that induces both systemic and mucosal immune responses. Methods Two separate clinical studies were conducted to evaluate the safety and immunogenicity of an oral NoV vaccine and NoV infection. The first study investigated an oral tablet vaccine based on a recombinant adenovirus vector expressing NoV VP1 (rAd-VP1). In the second study, a controlled NoV infection (Norwalk virus) was performed using a strain isolated and purified from an infected subject. Serum and PBMCs were collected pre- and post-immunization/infection. Serum immune responses were assessed using IgG/IgA ELISAs and blocking titer (BT50) assays. Cellular immune responses were evaluated using antibody-secreting cell (ASC) assays to quantitate norovirus-specific B cells. Flow cytometry was used to analyze the phenotype of circulating B and T cells. Results The rAd-VP1 vaccine was well tolerated whereas most subjects (56%) in the controlled infection study had significant gastroenteritis 2–4 days post-inoculation. Subjects in cohorts vaccinated 28 days apart with 1 × 1010 or 1 × 1011 IUs showed the highest rises in serum IgG and IgA titers compared with those immunized 2 or 7 days apart with a 1 × 1010 IU vaccine dose. Subjects in the 1 × 1011 IU vaccine dose cohort had a 6-fold rise in serum IgA and 4-fold rise in BT50 titers, with mean IgA and IgG ASC values of 698 and 389 counts, respectively. In comparison, NoV-challenged subjects showed an average of 2,072 IgA and 886 IgG ASC counts. Remarkably, flow cytometry analysis revealed that activated B- and T-cell responses were similar post-vaccination and post-infection, with significant expansion of T follicular cells, plasmablasts, mucosal homing B cells, and preferential activation of IgA B cells. Conclusion The phenotype of activated B and T cells induced post-immunization was similar to that induced post-infection, suggesting that an oral vaccine can induce comparable adaptive immune responses without the substantial adverse clinical events that occur from natural infection. Future work in dose ranging will aide in the development of a safe and efficacious oral NoV vaccine. Disclosures All Authors: No reported Disclosures.

scholarly journals Nonspecific activation of murine lymphocytes. VI. Mediation of synergistic interaction between T and B lymphocytes by a cell-associated, reciprocally acting lymphocyte proliferation helper.

1979 ◽  
Vol 149 (3) ◽  
pp. 644-657 ◽  
Author(s):  
M G Goodman ◽  
W O Weigle
Keyword(s):  
T Cells ◽  
B Cells ◽  
Lymphocyte Proliferation ◽  
Proliferative Response ◽  
Tritiated Thymidine ◽  
Cell Types ◽  
Physical Contact ◽  
Blast Transformation ◽  
Cellular Interactions ◽  
Spleen Cells

The mechanism by which B and T lymphocytes interact synergistically in the proliferative response to 2-mercaptoethanol (2-ME) as a mitogen was investigated in cultures of C3H/St spleen cells. The interaction between these cells required physical contact between the collaborating cell types, and was not mediated by the release of a soluble factor into the culture supernate. Sonicates of spleen cells which had been activated with optimal concentrations of 2-ME for 24 h and then washed extensively, stimulated the uptake of tritiated thymidine and morphological blast transformation of fresh, unstimulated cells. This activity was found to reside within the soluble fraction of the activated cells, and to activate cells optimally at a ratio of 1 naive cell: 1 activated cell-equivalent. This reciprocally-acting lymphocyte proliferation helper (RALPH) activity was produced by B cells as well as by T cells, with a kinetic peak at 48 h of culture. RALPH activity was produced by viable but not by nonviable cells incubated with 2-ME, and was nondialyzable. It could not be induced by the B-cell mitogens lipopolysaccharide, polyinosinic-polycytidilic acid, or purified protein derivative of tuberculin, or by the T-cell mitogen concanavalin A. RALPH isolated from T cells activated B cells exclusively, while that from B cells acted predominantly upon T cells, possibly with a nonspecific effect on B cells. A model for the cellular interactions involved in the amplification of the proliferative response to 2-ME is described.

Sign in / Sign up

Export Citation Format

Share Document