Machteld M. Tiemessen, Tracey J. Mitchell, Lisa Hendry, Sean J

Slides:

Advertisements

Similar presentations

Prevention and Mitigation of Experimental Autoimmune Encephalomyelitis by Murine β- Defensins via Induction of Regulatory T Cells Anika Bruhs, Thomas.

Advertisements

Depletion of Alloreactive Donor T Lymphocytes by CD95-Mediated Activation-Induced Cell Death Retains Antileukemic, Antiviral, and Immunoregulatory T Cell.

Cell-to-cell contact between activated CD4+ T lymphocytes and unprimed monocytes interferes with a TH1 response Miriam Wittmann, MD, Mareike Alter, Tanja.

Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathway by Kevin M. Elias, Arian Laurence,

Volume 136, Issue 4, Pages e3 (April 2009)

Increased Expression of CTLA-4 in Malignant T Cells from Patients with Mycosis Fungoides – Cutaneous T-Cell Lymphoma Henry K. Wong, Adam J. Wilson, Heather.

Impaired Responses of Peripheral Blood Mononuclear Cells to Staphylococcal Superantigen in Patients with Severe Atopic Dermatitis: A Role of T Cell Apoptosis

Volume 135, Issue 6, Pages (December 2008)

IL-31 Is Produced by the Malignant T-Cell Population in Cutaneous T-Cell Lymphoma and Correlates with CTCL Pruritus Elisha M. Singer, Daniel B. Shin,

CD90+ Human Dermal Stromal Cells Are Potent Inducers of FoxP3+ Regulatory T Cells Karin Pfisterer, Karoline M. Lipnik, Erhard Hofer, Adelheid Elbe-Bürger

Expansion of FOXP3high regulatory T cells by human dendritic cells (DCs) in vitro and after injection of cytokine-matured DCs in myeloma patients by Devi.

HLA-A*0201+ Plasmacytoid Dendritic Cells Provide a Cell-Based Immunotherapy for Melanoma Patients Caroline Aspord, Marie-Therese Leccia, Dimitri Salameire,

Efalizumab Therapy for Atopic Dermatitis Causes Marked Increases in Circulating Effector Memory CD4+ T Cells That Express Cutaneous Lymphocyte Antigen

The IL-17A-Producing CD8+ T-Cell Population in Psoriatic Lesional Skin Comprises Mucosa-Associated Invariant T Cells and Conventional T Cells Marcel.

Combined CD4+ Donor Lymphocyte Infusion and Low-Dose Recombinant IL-2 Expand FOXP3+ Regulatory T Cells following Allogeneic Hematopoietic Stem Cell Transplantation

Human CD4+CD25+ Cells in Combination with CD34+ Cells and Thymoglobulin to Prevent Anti-hematopoietic Stem Cell T Cell Alloreactivity Dolores Mahmud,

Induction and maintenance of allergen-specific FOXP3+ Treg cells in human tonsils as potential first-line organs of oral tolerance Oscar Palomares, PhD,

IL-13-Stimulated Human Keratinocytes Preferentially Attract CD4+CCR4+ T cells: Possible Role in Atopic Dermatitis Rahul Purwar, Thomas Werfel, Miriam.

Myeloid-Derived Suppressor Cells in Psoriasis Are an Expanded Population Exhibiting Diverse T-Cell–Suppressor Mechanisms Lauren Y. Cao, Jin-Sung Chung,

Hair Follicle Mesenchyme-Associated PD-L1 Regulates T-Cell Activation Induced Apoptosis: A Potential Mechanism of Immune Privilege Xiaojie Wang, Alexandra.

Volume 141, Issue 3, Pages (September 2011)

Α-MSH-Stimulated Tolerogenic Dendritic Cells Induce Functional Regulatory T Cells and Ameliorate Ongoing Skin Inflammation Matteo Auriemma, Thomas Brzoska,

Increased Soluble CD226 in Sera of Patients with Cutaneous T-Cell Lymphoma Mediates Cytotoxic Activity against Tumor Cells via CD155 Naomi Takahashi,

Liisa Väkevä, Annamari Ranki Journal of Investigative Dermatology

Norito Katoh, Fujiko Soga, Takeshi Nara, Koji Masuda, Saburo Kishimoto

Volume 137, Issue 5, Pages (November 2009)

Langerhans Cells from Human Cutaneous Squamous Cell Carcinoma Induce Strong Type 1 Immunity Hideki Fujita, Mayte Suárez-Fariñas, Hiroshi Mitsui, Juana.

Volume 85, Issue 3, Pages (March 2014)

CD4+CD25+FOXP3+ malignant T cells in Sézary syndrome are not necessarily functional regulatory T cells David A. Wada, MD, Mark R. Pittelkow, MD, Nneka.

Targeting PKC in Human T Cells Using Sotrastaurin (AEB071) Preserves Regulatory T Cells and Prevents IL-17 Production Xuehui He, Hans J.P.M. Koenen,

HLA-A*0201+ Plasmacytoid Dendritic Cells Provide a Cell-Based Immunotherapy for Melanoma Patients Caroline Aspord, Marie-Therese Leccia, Dimitri Salameire,

Human CD34+ blood cells induce T-cell unresponsiveness to specific alloantigens only under costimulatory blockade Mario Arpinati, Carolina Terragna,

Allospecific Tregs Expanded After Anergization Remain Suppressive in Inflammatory Conditions but Lack Expression of Gut-homing Molecules Eleni Kotsiou,

The Human Skin–Associated Autoantigen α-NAC Activates Monocytes and Dendritic Cells via TLR-2 and Primes an IL-12-Dependent Th1 Response Susanne Hradetzky,

Induction of T-Cell Responses against Cutaneous T-Cell Lymphomas Ex Vivo by Autologous Dendritic Cells Transfected with Amplified Tumor mRNA Xiao Ni,

T Cell Epitope-Specific Defects in the Immune Response to Cat Allergen in Patients with Atopic Dermatitis Raquel Carneiro, Amanda Reefer, Barbara Wilson,

Suzanne M. Morgan, Elizabeth Hodges, Tracey J

A Regulatory Feedback between Plasmacytoid Dendritic Cells and Regulatory B Cells Is Aberrant in Systemic Lupus Erythematosus Madhvi Menon, Paul A. Blair,

CD4+ T Cells in Lymph Nodes of UVB-Irradiated Mice Suppress Immune Responses to New Antigens Both In Vitro and In Vivo Shelley Gorman, Jamie W.-Y. Tan,

Human Plasmacytoid Dendritic Cells Express Receptors for Anaphylatoxins C3a and C5a and Are Chemoattracted to C3a and C5a Ralf Gutzmer, Brigitta Köther,

Volume 135, Issue 1, Pages (July 2008)

Volume 28, Issue 6, Pages (June 2008)

Volume 24, Issue 2, Pages (February 2006)

Indoleamine 2,3-Dioxygenase Activity Contributes to Local Immune Suppression in the Skin Expressing Human Papillomavirus Oncoprotein E7 Deepak Mittal,

Shelley Gorman, Melinda A. Judge, Prue H. Hart

Abnormal Natural Killer Cell Function in Systemic Sclerosis: Altered Cytokine Production and Defective Killing Activity Mayuka Horikawa, Minoru Hasegawa,

Volume 128, Issue 7, Pages (June 2005)

Heterogeneous MHC II Restriction Pattern of Autoreactive Desmoglein 3 Specific T Cell Responses in Pemphigus Vulgaris Patients and Normals Michael Hertl,

Demonstration of circulating allergen-specific CD4+CD25highFoxp3+ T-regulatory cells in both nonatopic and atopic individuals Laura Maggi, BSc, Veronica.

PPARδ Is a Type 1 IFN Target Gene and Inhibits Apoptosis in T Cells

CD127low/- and FoxP3+ Expression Levels Characterize Different Regulatory T-Cell Populations in Human Peripheral Blood Sandra Klein, Cosima C. Kretz,

MHC-Dependent and -Independent Activation of Human Nickel-Specific CD8+ Cytotoxic T Cells from Allergic Donors1 Corinne Moulon, Doris Wild, Hans Ulrich.

Human CD4+ T Lymphocytes with Remarkable Regulatory Functions on Dendritic Cells and Nickel-Specific Th1 Immune Responses Andrea Cavani, Francesca Nasorri,

FOXP3+CD25− Tumor Cells with Regulatory Function in Sézary Syndrome

Kim L. Kroeze, Wouter J. Jurgens, Behrouz Z. Doulabi, Florine J

Serotonin Activates Human Monocytes and Prevents Apoptosis

IL-4 and IL-13 Alter Plasmacytoid Dendritic Cell Responsiveness to CpG DNA and Herpes Simplex Virus-1 Jurjen Tel, Ruurd Torensma, Carl G. Figdor, I.

A.K.I. Kuroki, Masayuki Iyoda, Takanori Shibata, Tetsuzo Sugisaki

Eric C. Vonderheid, Christine M

Dimethylfumarate Induces Immunosuppression via Glutathione Depletion and Subsequent Induction of Heme Oxygenase 1 Joachim C.U. Lehmann, Joanna J. Listopad,

Curcumin Selectively Induces Apoptosis in Cutaneous T-Cell Lymphoma Cell Lines and Patients’ PBMCs: Potential Role for STAT-3 and NF-κB Signaling Chunlei.

Volume 71, Issue 11, Pages (June 2007)

Insights into Gene Modulation by Therapeutic TNF and IFNγ Antibodies: TNF Regulates IFNγ Production by T Cells and TNF-Regulated Genes Linked to Psoriasis.

A Role for Regulatory T Cells in Cutaneous T-Cell Lymphoma; Induction of a CD4+CD25+Foxp3+ T-Cell Phenotype Associated with HTLV-1 Infection Patrick.

Volume 142, Issue 7, Pages e6 (June 2012)

Variable CD7 Expression on T Cells in the Leukemic Phase of Cutaneous T Cell Lymphoma (Sézary Syndrome) Eric C. Vonderheid, Amy Kotecha, Christine M.

Regulation of IL-13 Receptors in Human Keratinocytes

T Helper Type 2-Biased Natural Killer Cell Phenotype in Patients with Pemphigus Vulgaris Hayato Takahashi, Masayuki Amagai, Akiko Tanikawa, Shigeaki.

Patient Tregs express normal levels of suppression.

The Majority of Epidermal T Cells in Psoriasis Vulgaris Lesions can Produce Type 1 Cytokines, Interferon-γ, Interleukin-2, and Tumor Necrosis Factor-α,

Presentation transcript:

Lack of Suppressive CD4+CD25+FOXP3+ T Cells in Advanced Stages of Primary Cutaneous T-Cell Lymphoma Machteld M. Tiemessen, Tracey J. Mitchell, Lisa Hendry, Sean J. Whittaker, Leonie S. Taams, Susan John Journal of Investigative Dermatology Volume 126, Issue 10, Pages 2217-2223 (October 2006) DOI: 10.1038/sj.jid.5700371 Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 The anergic phenotype of CD4+ T cells from CTCL patients is not owing to an overall increase in CD4+CD25+ T cells. CD4+ T cells were isolated from PBMC of HC and CTCL patients via MACS. (a) CD4+ T cells were stimulated with anti-CD3 mAb (50ng/ml) and APC, and T-cell proliferation was measured by 3H-thymidine incorporation. Data are depicted as mean c.p.m.±SEM, n=10 independent experiments. (b) Representative dot plots of peripheral blood lymphocytes from HC versus a CTCL patient showing the percentage of CD4+CD25+total and CD4+CD25+bright T cells in CD4+ T cells; the square region indicates CD4+CD25bright T cells. (c) The percentages of CD4+CD25+total and CD4+CD25+bright T cells in the CD4+ T-cell fraction are shown for each individual HC and CTCL patient. Journal of Investigative Dermatology 2006 126, 2217-2223DOI: (10.1038/sj.jid.5700371) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Dichotomy in suppressive activity of CD4+CD25+ Tregs from CTCL patients. (a) CD4+CD25+ T cells were isolated from phosphate buffer from HC and CTCL patients by MACS. Representative dot plots show the percentage CD4+CD25+ T cells from HC and CTCL patients before and after purification. (b) The relative mRNA expression of CD25 in purified CD4+CD25− and CD4+CD25+ T-cell subsets from HC and CTCL patients was determined by real-time PCR. Results are shown as the mean±SEM of eight independent experiments. (c) Isolated CD4+CD25− T cells were cultured with anti-CD3 mAb and irradiated autologous PBMC in the absence (black bars, 1:0 ratio) or presence (open bars, 1:1 ratio) of autologous CD4+CD25+ T cells. Results of three representative independent experiments are shown: one CTCL patient with non-suppressive CD4+CD25+ T cells (CTCL3), one CTCL patient with suppressive CD4+CD25+ T cells (CTCL6), and one representative HC (HC9). Journal of Investigative Dermatology 2006 126, 2217-2223DOI: (10.1038/sj.jid.5700371) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Lack of suppressive function in CD4+CD25+ Tregs in CTCL patients is associated with significantly lower Foxp3 mRNA expression. (a) The relative mRNA expression levels of Foxp3, (b) CTLA-4, and (c) T-plastin in CD4+CD25− and CD4+CD25+ T cells were assessed by real-time PCR. The mean±SEM of the mRNA expression is shown for HCs (n=8), suppressive CTCL patients (n=4), and non-suppressive CTCL patients (n=4). Significant differences are indicated in the figures; ND, not detected. Journal of Investigative Dermatology 2006 126, 2217-2223DOI: (10.1038/sj.jid.5700371) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 The defect in Treg-mediated regulation lies within the CD4+CD25+ T-cell population. CD4+CD25+ or CD4+CD25− T cells from (a) non-suppressive or (b) suppressive CTCL patients were tested for their capacity to suppress the proliferation of allogeneic T cells derived from HC. CD4+CD25− HC T cells were cultured alone (black bars, 1:0), in the presence of CD4+CD25+ CTCL T cells (white bars, 1:1 ratio) or CD4+CD25− CTCL T cells (hatched bars, 1:1 ratio). (c) CD4+CD25−T-cells from a non-suppressive patient were cultured in the absence (black bar, 1:0) or presence of allogeneic CD4+CD25+ T cells derived from HC (white bar, 1:1 ratio). The suppressive activity is indicated by percentage inhibition in each graph. The intrinsic suppressive activity of the CD4+CD25+T cells in the corresponding autologous system were 0, 89, and 40% for non-suppressive CTCLs, suppressive CTCLs, and HCs, respectively. One of the two independent experiments is shown. Journal of Investigative Dermatology 2006 126, 2217-2223DOI: (10.1038/sj.jid.5700371) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions