CD4 T Cell Subset Profiling in Biliary Atresia Reveals ICOS- Regulatory T Cells as a Favourable Prognostic Factor

Diabetes was induced in a normal nonautoimmune rat strain by rendering the animals relatively T cell deficient using a protocol of adult thymectomy and sublethal gamma irradiation. All male rats and 70% of females developed an acute syndrome with severe loss of weight and hyperglycemia. Diabetes in these lymphopoenic rats was associated with extensive insulitis involving CD4+ and CD8+ T cells and macrophages. The CD8+ T cells were essential for the development of diabetes but not insulitis. The autoimmune diabetes and insulitis were completely prevented by the injection of a particular CD4+ T cell subset, isolated from healthy syngeneic donors, of the phenotype CD45RClow T cell receptor alpha/beta+ RT6+ Thy-1- OX-40-. Cells of this protective phenotype, which make up about 5% of thoracic duct lymphocytes, were found to provide help for secondary antibody responses and produce interleukin 2 (IL-2) and IL-4, but no interferon gamma, on in vitro activation. These data provide evidence for the presence of autoreactive T cells in the normal immune system of the rat and reveal that in the intact animal these cells are prevented from expressing their autoreactive potential by other T cells.

Download Full-text

Regulatory T cells in experimental allergic encephalomyelitis. I. Frequency and specificity analysis in normal and immune rats of a T cell subset that inhibits disease

International Immunology ◽

10.1093/intimm/11.3.307 ◽

1999 ◽

Vol 11 (3) ◽

pp. 307-315 ◽

Cited By ~ 18

Author(s):

D. Sun

Keyword(s):

T Cells ◽

T Cell ◽

Regulatory T Cells ◽

Experimental Allergic Encephalomyelitis ◽

Cell Subset ◽

Allergic Encephalomyelitis ◽

T Cell Subset ◽

Experimental Allergic

Download Full-text

Distinctions Between CD8+ and CD4+ T-Cell Regenerative Pathways Result in Prolonged T-Cell Subset Imbalance After Intensive Chemotherapy

Blood ◽

10.1182/blood.v89.10.3700.3700_3700_3707 ◽

1997 ◽

Vol 89 (10) ◽

pp. 3700-3707 ◽

Cited By ~ 7

Author(s):

Crystal L. Mackall ◽

Thomas A. Fleisher ◽

Margaret R. Brown ◽

Mary P. Andrich ◽

Clara C. Chen ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cd4 T Cells ◽

Cell Subset ◽

Cd8 T Cell ◽

Cell Number ◽

Cd4 T Cell ◽

Cell Regeneration ◽

Intensive Chemotherapy ◽

T Cell Subset

Rapid recovery of CD4+ T cells after intensive chemotherapy is limited by an age-dependent decline in thymopoiesis. Here we sought to determine whether similar limitations exist for CD8+ T-cell regeneration. After intensive chemotherapy, CD8+ T cells had a faster effective doubling time than CD4+ T cells (median, 12.6 v 28.2 days, P < .05). Accordingly, at 3 months posttherapy, mean CD8+ T-cell number had returned to baseline, whereas mean CD4+ T-cell number was only 35% of pretherapy values (P < .05). These differences were primarily due to very rapid expansion of CD8+CD57+ and CD8+CD28− subsets. At 3 months posttherapy, there was no relationship between age and CD8+ T-cell number (R = −.02), whereas CD4+ T-cell number was inversely related to age (R = −.66) and there were no discernible differences in CD8+ recovery among patients with or without thymic enlargement, whereas CD4+ recovery was enhanced in patients with thymic enlargement after chemotherapy (P < .01). Therefore thymic-independent pathways of T-cell regeneration appear to rapidly regenerate substantial numbers of CD8+, but not CD4+ T cells, resulting in prolonged T-cell subset imbalance after T-cell depletion. These inherent distinctions between CD4+v CD8+ T-cell regeneration may have significant implications for immunotherapeutic strategies undertaken to eradicate minimal residual neoplastic disease after cytoreductive chemotherapy.

Download Full-text

B Cell Presentation of Chlamydia Antigen Selects Out Protective CD4γ13 T Cells: Implications for Genital Tract Tissue-Resident Memory Lymphocyte Clusters

Infection and Immunity ◽

10.1128/iai.00614-17 ◽

2017 ◽

Vol 86 (2) ◽

Cited By ~ 9

Author(s):

Raymond M. Johnson ◽

Hong Yu ◽

Norma Olivares Strank ◽

Karuna Karunakaran ◽

Ying Zhu ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

B Cell ◽

Genital Tract ◽

Cell Subset ◽

Cd4 T Cell ◽

Content Type ◽

T Cell Subset ◽

Ifn Γ

ABSTRACTSurveillance and defense of the enormous mucosal interface with the nonsterile world are critical to protecting the host from a wide range of pathogens.Chlamydia trachomatisis an intracellular bacterial pathogen that replicates almost exclusively in the epithelium of the reproductive tract. The fallopian tubes and vagina are poorly suited to surveillance and defense, with limited immune infrastructure positioned near the epithelium. However, a dynamic process during clearing primary infections leaves behind new lymphoid clusters immediately beneath the epithelium. These memory lymphocyte clusters (MLCs) harboring tissue-resident memory (Trm) T cells are presumed to play an important role in protection from subsequent infections. Histologically, humanChlamydiaMLCs have prominent B cell populations. We investigated the status of genital tract B cells duringC. muridaruminfections and the nature of T cells recovered from immune mice using immune B cells as antigen-presenting cells (APCs). These studies revealed a genital tract plasma B cell population and a novel genital tract CD4 T cell subset producing both gamma interferon (IFN-γ) and interleukin-13 (IL-13). A panel of CD4 T cell clones and microarray analysis showed that the molecular fingerprint of CD4γ13 T cells includes a Trm-like transcriptome. Adoptive transfer of aChlamydia-specific CD4γ13 T cell clone completely prevented oviduct immunopathology without accelerating bacterial clearance. Existence of a CD4γ13 T cell subset provides a plausible explanation for the observation that human peripheral blood mononuclear cell (PBMC)Chlamydia-specific IFN-γ and IL-13 responses predict resistance to reinfection.

Download Full-text

Functional assessment and specific depletion of alloreactive human T cells using flow cytometry

Blood ◽

10.1182/blood-2004-05-1918 ◽

2004 ◽

Vol 104 (12) ◽

pp. 3429-3436 ◽

Cited By ~ 69

Author(s):

Sergio L. R. Martins ◽

Lisa S. St. John ◽

Richard E. Champlin ◽

Eric D. Wieder ◽

John McMannis ◽

...

Keyword(s):

Flow Cytometry ◽

T Cells ◽

T Cell ◽

Cell Subset ◽

Cd4 T Cell ◽

Solid Organ ◽

Activation Markers ◽

Human Virus ◽

T Cell Subset ◽

Viral Antigens

Human T-cell alloreactivity plays an important role in many disease processes, including the rejection of solid organ grafts and graft-versus-host disease (GVHD) following allogeneic stem cell transplantation. To develop a better understanding of the T cells involved in alloreactivity in humans, we developed a cytokine flow cytometry (CFC) assay that enabled us to characterize the phenotypic and functional characteristic of T cells responding to allogeneic stimuli. Using this approach, we determined that most T-cell alloreactivity resided within the CD4+ T-cell subset, as assessed by activation marker expression and the production of effector cytokines (eg, tumor necrosis factor α [TNF]α) implicated in human GVHD. Following prolonged stimulation in vitro using either allogeneic stimulator cells or viral antigens, we found that coexpression of activation markers within the CD4+ T-cell subset occurred exclusively within a subpopulation of T cells that significantly increased their surface expression of CD4. We then developed a simple sorting strategy that exploited these phenotypic characteristics to specifically deplete alloreactive T cells while retaining broad specificity for other stimuli, including viral antigens and third-party alloantigens. This approach also was applied to specifically enrich or deplete human virus-specific T cells.

Download Full-text

Single cell sequencing reveals expanded cytotoxic CD4+ T cells and two states of peripheral helper T cells in synovial fluid of ACPA+ RA patients

10.1101/2021.05.28.21255902 ◽

2021 ◽

Author(s):

Alexandra Argyriou ◽

Marc H Wadsworth ◽

Adrian Lendvai ◽

Stephen M Christensen ◽

Aase Hensvold ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Synovial Fluid ◽

Single Cell ◽

Cd4 T Cells ◽

Cell Subset ◽

T Cell Subsets ◽

Cd4 T Cell ◽

T Cell Subset ◽

Single Cell Sequencing

Rheumatoid arthritis is an autoimmune disease affecting the synovial joints where different subsets of CD4+ T cells are suspected to play a pathogenic role. So far, our understanding of the contribution of cytotoxic CD4+ T cells is incomplete, particularly in the context of the recently described peripheral helper T-cell subset (TPH). Here, using single cell sequencing and multi-parameter flow cytometry, we show that cytotoxic CD4+ T cells are enriched in synovial fluid of anti-citrullinated peptides antibody (ACPA)-positive RA patients. We identify two distinct TPH states differentially characterized by the expression of CXCL13 and PRDM1, respectively. Our data reveal that the adhesion G-Protein Coupled Receptor 56 (GPR56), a marker of circulating cytotoxic cells, delineates the synovial TPH CD4+ T-cell subset. At the site of inflammation, GPR56+CD4+ T cells expressed the tissue-resident memory markers LAG-3, CXCR6 and CD69. Further, TCR clonality analysis revealed that most expanded clones in SF are contained within the cytotoxic and the CXCL13+ TPH CD4+ T-cell populations. Finally, the detection of common TCRs between the two TPH and cytotoxic CD4+ T-cell clusters suggest a shared differentiation. Our study provides comprehensive immunoprofiling of the heterogenous T-cell subsets at the site of inflammation in ACPA+ RA and suggests GPR56 as a therapeutic target to modulate TPH cells and cytotoxic CD4+ T cell function

Download Full-text

Distinctions Between CD8+ and CD4+ T-Cell Regenerative Pathways Result in Prolonged T-Cell Subset Imbalance After Intensive Chemotherapy

Blood ◽

10.1182/blood.v89.10.3700 ◽

1997 ◽

Vol 89 (10) ◽

pp. 3700-3707 ◽

Cited By ~ 268

Author(s):

Crystal L. Mackall ◽

Thomas A. Fleisher ◽

Margaret R. Brown ◽

Mary P. Andrich ◽

Clara C. Chen ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cd4 T Cells ◽

Cell Subset ◽

Cd8 T Cell ◽

Cell Number ◽

Cd4 T Cell ◽

Cell Regeneration ◽

Intensive Chemotherapy ◽

T Cell Subset

Abstract Rapid recovery of CD4+ T cells after intensive chemotherapy is limited by an age-dependent decline in thymopoiesis. Here we sought to determine whether similar limitations exist for CD8+ T-cell regeneration. After intensive chemotherapy, CD8+ T cells had a faster effective doubling time than CD4+ T cells (median, 12.6 v 28.2 days, P < .05). Accordingly, at 3 months posttherapy, mean CD8+ T-cell number had returned to baseline, whereas mean CD4+ T-cell number was only 35% of pretherapy values (P < .05). These differences were primarily due to very rapid expansion of CD8+CD57+ and CD8+CD28− subsets. At 3 months posttherapy, there was no relationship between age and CD8+ T-cell number (R = −.02), whereas CD4+ T-cell number was inversely related to age (R = −.66) and there were no discernible differences in CD8+ recovery among patients with or without thymic enlargement, whereas CD4+ recovery was enhanced in patients with thymic enlargement after chemotherapy (P < .01). Therefore thymic-independent pathways of T-cell regeneration appear to rapidly regenerate substantial numbers of CD8+, but not CD4+ T cells, resulting in prolonged T-cell subset imbalance after T-cell depletion. These inherent distinctions between CD4+v CD8+ T-cell regeneration may have significant implications for immunotherapeutic strategies undertaken to eradicate minimal residual neoplastic disease after cytoreductive chemotherapy.

Download Full-text