Dexamethasone Alters Tracheal Aspirate T-Cell Phenotype in Ventilated Preterm Infants

Postnatal corticosteroids improve respiratory status and facilitate respiratory support weaning in preterm infants with bronchopulmonary dysplasia (BPD). Older literature describes characteristic cytokine profiles in tracheal aspirates (TA) of BPD patients which are altered with corticosteroids. Corticosteroids also influence peripheral blood T-cell presence. However, little is known regarding TA T-cell phenotype and cytokine production before or after exogenous corticosteroids. We hypothesized that postnatal dexamethasone alters the TA T-cell cytokine profiles of preterm infants. TA samples were collected from 14 infants born from 23 0/7 to 28 6/7 weeks who were mechanically ventilated for at least 14 days. Samples were collected up to 72 h before a ten-day dexamethasone course and again 1 to 3 calendar days after dexamethasone initiation. The primary outcome was change in T cell populations present in TA and their intracellular cytokine profile after dexamethasone treatment, ascertained via flow cytometry. Following dexamethasone treatment, there were significant decreases in respiratory severity score (RSS), percent CD4+IL-6+ cells, CD8+IL-6+ cells, CXCR3+IL-6+ cells, and CXCR3+IL-2+ cells and total intracellular IFN-γ in TA. RSS significantly correlated with TA percent CD4+IL-6+ cells. To our knowledge, this is the first study demonstrating that dexamethasone reduced T-cell IL-6 and this reduction was associated with improved RSS in pre-term infants with evolving BPD.

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Faculty Opinions recommendation of Calcium-mediated shaping of naive CD4 T-cell phenotype and function.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732298967.793543036 ◽

2018 ◽

Author(s):

Michael L Dustin

Keyword(s):

T Cell ◽

Cd4 T Cell ◽

Cell Phenotype ◽

And Function

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Characterisation of the T-cell response to Ebola virus glycoprotein amongst survivors of the 2013–16 West Africa epidemic

Nature Communications ◽

10.1038/s41467-021-21411-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

T. R. W. Tipton ◽

Y. Hall ◽

J. A. Bore ◽

A. White ◽

L. S. Sibley ◽

...

Keyword(s):

T Cell ◽

West Africa ◽

Cell Response ◽

Ebola Virus ◽

Medical Condition ◽

Virus Disease ◽

T Cell Response ◽

Ebola Virus Disease ◽

Cell Phenotype ◽

T Cell Epitopes

AbstractZaireebolavirus (EBOV) is a highly pathogenic filovirus which can result in Ebola virus disease (EVD); a serious medical condition that presents as flu like symptoms but then often leads to more serious or fatal outcomes. The 2013–16 West Africa epidemic saw an unparalleled number of cases. Here we show characterisation and identification of T cell epitopes in surviving patients from Guinea to the EBOV glycoprotein. We perform interferon gamma (IFNγ) ELISpot using a glycoprotein peptide library to identify T cell epitopes and determine the CD4+ or CD8+ T cell component response. Additionally, we generate data on the T cell phenotype and measure polyfunctional cytokine secretion by these antigen specific cells. We show candidate peptides able to elicit a T cell response in EBOV survivors and provide inferred human leukocyte antigen (HLA) allele restriction. This data informs on the long-term T cell response to Ebola virus disease and highlights potentially important immunodominant peptides.

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The Impact of Exercise Serum on Selected Parameters of CD4+ T Cell Metabolism

Immuno ◽

10.3390/immuno1030008 ◽

2021 ◽

Vol 1 (3) ◽

pp. 119-131

Author(s):

Jana Palmowski ◽

Kristina Gebhardt ◽

Thomas Reichel ◽

Torsten Frech ◽

Robert Ringseis ◽

...

Keyword(s):

T Cells ◽

Oxygen Consumption ◽

T Cell ◽

Real Time ◽

Cd4 T Cells ◽

Cell Metabolism ◽

Cd4 T Cell ◽

Autologous Serum ◽

Cell Phenotype ◽

The Impact

CD4+ T cells are sensitive to peripheral changes of cytokine levels and metabolic substrates such as glucose and lactate. This study aimed to analyze whether factors released after exercise alter parameters of human T cell metabolism, specifically glycolysis and oxidative phosphorylation. We used primary human CD4+ T cells activated in the presence of autologous serum, which was collected before (CO) and after a 30-min exercise intervention (EX). In the course of activation, cells and supernatants were analyzed for cell viability and diameter, real-time oxygen consumption by using PreSens Technology, mRNA expression of glycolytic enzymes and complexes of the electron transport chain by real-time PCR, glucose, and lactate levels in supernatants, and in vitro differentiation by flow cytometry. EX did not alter T cell phenotype, viability, or on-blast formation. Similarly, no difference between CO and EX were found for CD4+ T cell activation and cellular oxygen consumption. In contrast, higher levels of glucose were found after 48 h activation in EX conditions. T cells activated in autologous exercise serum expressed lower HK1 mRNA and higher IFN-γ receptor 1. We suggest that the exercise protocol used was not sufficient to destabilize the immune metabolism of T cells. Therefore, more intense and prolonged exercise should be used in future studies.

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Impacts of HIV infection on Vγ2Vδ2 T cell phenotype and function: a mechanism for reduced tumor immunity in AIDS

Journal of Leukocyte Biology ◽

10.1189/jlb.1207847 ◽

2008 ◽

Vol 84 (2) ◽

pp. 371-379 ◽

Cited By ~ 26

Author(s):

Jean-Saville Cummings ◽

Cristiana Cairo ◽

Cheryl Armstrong ◽

Charles E. Davis ◽

C. David Pauza

Keyword(s):

T Cell ◽

Hiv Infection ◽

Tumor Immunity ◽

Cell Phenotype ◽

And Function

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Primary Cutaneous CD30-Positive Anaplastic Large Cell Lymphoma in Childhood: Report of 4 Cases and Review of the Literature

Pediatric and Developmental Pathology ◽

10.1007/s10024-004-8087-6 ◽

2005 ◽

Vol 8 (1) ◽

pp. 52-60 ◽

Cited By ~ 39

Author(s):

Shimareet Kumar ◽

Stefania Pittaluga ◽

Mark Raffeld ◽

Michael Guerrera ◽

Nita L. Seibel ◽

...

Keyword(s):

T Cell ◽

Anaplastic Large Cell Lymphoma ◽

Cell Lymphoma ◽

Subcutaneous Tissue ◽

Pediatric Population ◽

Large Cell ◽

Lymphoid Cells ◽

Cell Phenotype ◽

Anaplastic Lymphoma ◽

Large Cell Lymphoma

We present the clinicopathologic findings in 4 children with primary cutaneous anaplastic large cell lymphoma (C-ALCL). The patients ranged in age from 13 months to 8 years, with 3 females and 1 male. All presented with a rapidly enlarging mass involving the skin and subcutaneous tissue. Histologic evaluation showed sheets of large pleomorphic lymphoid cells that were diffusely and strongly CD30+. Tumor cells were CD45+ in 1 of 4 cases. Cells were of T-cell phenotype, with variable positivity for CD3 (3 of 4 cases) and CD5 (2 of 4 cases). All 4 cases were positive for CD4 and clusterin. Staining for anaplastic lymphoma kinase was negative in all cases. No evidence of systemic involvement was noted at initial presentation or over a follow-up of 5 to 78 months, although 3 patients had cutaneous recurrences. Primary C-ALCL has only rarely been described in the pediatric population. The high-grade histologic appearance of this lymphoma belies its generally favorable clinical course and prognosis. Recognition of this entity and its differentiation from other T-cell lymphomas that secondarily involve the skin is important to avoid unnecessarily aggressive therapy in these children.

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CD79a+ T-Cell Lymphoblastic Lymphoma With Coexisting Langerhans Cell Histiocytosis

Archives of Pathology & Laboratory Medicine ◽

10.5858/2001-125-0958-ctcllw ◽

2001 ◽

Vol 125 (7) ◽

pp. 958-960

Author(s):

Shiyong Li ◽

Michael J. Borowitz

Keyword(s):

T Cell ◽

Langerhans Cell Histiocytosis ◽

Close Association ◽

Cervical Lymphadenopathy ◽

Lymphoblastic Lymphoma ◽

Langerhans Cell ◽

Terminal Deoxynucleotidyl Transferase ◽

Simultaneous Occurrence ◽

Cell Phenotype ◽

Malignant Neoplasms

Abstract Although there is a close association between Langerhans cell histiocytosis and malignant neoplasms, simultaneous occurrence of lymphoblastic lymphoma and Langerhans cell histiocytosis in the same lymph node is an extremely rare finding. Herein, we describe such a case in a 26-year-old woman who presented with progressive cervical lymphadenopathy. The lymphoma cells have an immature T-cell phenotype (terminal deoxynucleotidyl transferase+, HLA-DR+, CD34+, CD38+, and CD7+) with expression of both CD3 and CD79a on immunohistochemical stain. The Langerhans cells are present focally with the characteristic morphologic features and immunophenotype (CD1a+ and S100+). The significance of CD79a coexpression in T-cell lymphoblastic lymphoma and the association between lymphoblastic lymphoma and Langerhans cell histiocytosis are discussed.

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Combination cancer immunotherapy targeting PD-1 and GITR can rescue CD8+T cell dysfunction and maintain memory phenotype

Science Immunology ◽

10.1126/sciimmunol.aat7061 ◽

2018 ◽

Vol 3 (29) ◽

pp. eaat7061 ◽

Cited By ~ 44

Author(s):

Bei Wang ◽

Wen Zhang ◽

Vladimir Jankovic ◽

Jacquelynn Golubov ◽

Patrick Poon ◽

...

Keyword(s):

T Cells ◽

Cell Death ◽

T Cell ◽

Programmed Cell Death ◽

Cancer Immunotherapy ◽

Effector Memory ◽

Cell Phenotype ◽

Checkpoint Inhibition ◽

Cell Dysfunction ◽

T Cell Dysfunction

Most patients with cancer do not develop durable antitumor responses after programmed cell death protein 1 (PD-1) or programmed cell death ligand 1(PD-L1) checkpoint inhibition monotherapy because of an ephemeral reversal of T cell dysfunction and failure to promote long-lasting immunological T cell memory. Activating costimulatory pathways to induce stronger T cell activation may improve the efficacy of checkpoint inhibition and lead to durable antitumor responses. We performed single-cell RNA sequencing of more than 2000 tumor-infiltrating CD8+T cells in mice receiving both PD-1 and GITR (glucocorticoid-induced tumor necrosis factor receptor–related protein) antibodies and found that this combination synergistically enhanced the effector function of expanded CD8+T cells by restoring the balance of key homeostatic regulators CD226 and T cell immunoreceptor with Ig and ITIM domains (TIGIT), leading to a robust survival benefit. Combination therapy decreased CD8+T cell dysfunction and induced a highly proliferative precursor effector memory T cell phenotype in a CD226-dependent manner. PD-1 inhibition rescued CD226 activity by preventing PD-1–Src homology region 2 (SHP2) dephosphophorylation of the CD226 intracellular domain, whereas GITR agonism decreased TIGIT expression. Unmasking the molecular pathways driving durable antitumor responses will be essential to the development of rational approaches to optimizing cancer immunotherapy.

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An intrinsic B cell defect is required for the production of autoantibodies in the lpr model of murine systemic autoimmunity.

Journal of Experimental Medicine ◽

10.1084/jem.173.6.1441 ◽

1991 ◽

Vol 173 (6) ◽

pp. 1441-1449 ◽

Cited By ~ 129

Author(s):

E S Sobel ◽

T Katagiri ◽

K Katagiri ◽

S C Morris ◽

P L Cohen ◽

...

Keyword(s):

Bone Marrow ◽

T Cell ◽

B Cells ◽

Lupus Erythematosus ◽

Immunofluorescence Assay ◽

Total Serum ◽

Enzyme Linked Immunosorbent Assay ◽

Cell Phenotype ◽

Autoantibody Production ◽

Systemic Autoimmunity

Mice homozygous for the gene lpr develop marked lymphadenopathy and a spectrum of autoantibodies closely resembling that of human systemic lupus erythematosus. The unusual T cell phenotype of the expanded lymphocyte population and the T-dependence of several antibodies in this strain have suggested that primary T cell abnormalities underlie the autoimmune syndrome. Using double chimeras, we now show that expression of the lpr gene in B cells is absolutely necessary for autoantibody production. Combinations of anti-Thy 1.2 + C' treated bone marrow from congenic strains of C57BL/6 mice, differing only at the immunoglobulin heavy chain (Igh) and lpr loci, were transferred into lethally irradiated B6/lpr mice. Double chimerism was documented by allotype-specific surface IgD and IgM immunofluorescence assay of peripheral blood and by allotype-specific enzyme-linked immunosorbent assay for total IgM in serum. Despite the presence of both +/+ and lpr B cells, IgM and IgG2a anti-chromatin as well as IgM anti-IgG were entirely the products of lpr B cells. Total serum IgG2a and IgG1 were also dominated by the lpr phenotype but not to the same extent. A similar experiment using B6/lpr-Igha recipients confirmed these findings. Additional experiments in which B6/lpr recipients were infused with ratios of donor bone marrow favoring B6.C20 +/+ over B6/lpr showed that even though +/+ B cells were overrepresented, autoantibodies were only of the lpr allotype. In addition, in the presence of lpr B cells, normal B cells showed little response to an exogenous, T cell-dependent antigen. The data thus indicate that lpr B cells manifest an intrinsic abnormality which is essential for autoantibody production in the lpr model.

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