Tolerogenic dendritic cells inhibit antiphospholipid syndrome derived effector/memory CD4+ T cell response to β2GPI

ObjectivesThe importance of β2-glycoprotein I (β2GPI)-specific CD4+ T cells in the development of pathogenic processes in patients with antiphospholipid syndrome (APS) and APS mouse models is well established. Therefore, our objective is to manipulate the β2GPI specific CD4+ T cells using tolerogenic dendritic cells (tDCs) to induce tolerance. We aim to evaluate the capability of tDCs to induce antigen-specific tolerance in effector/memory T cells from patients with APS and to elucidate the involved mechanism.MethodsDCs and tDCs were produced from patients with APS peripheral-blood-monocytes, using specific cytokines. β2GPI-specific tolerance induction was investigated by coculturing control DC (cDC) or tDC, β2GPI-loaded, with autologous effector/memory T cells, evaluating the proliferative response, phenotype, cytokines secretion, viability and regulatory T cells.ResultsHuman monocyte-derived DCs treated with interleukin (IL)-10 and transforming growth factor β-1 (10/TGF-DC) induced β2GPI-specific-unresponsiveness in effector/memory CD4+ T cells (46.5%±26.0 less proliferation) in 16 of 20 analysed patients with APS, without affecting the proliferative response to an unrelated candidin. In five analysed patients, 10/TGF-DC-stimulated T cells acquired an IL-2lowinterferon γlowIL-10high cytokine profile, with just a propensity to express higher numbers of Foxp3+CTLA-4+ cells, but with an evident suppressive ability. In four of 10 analysed patients, 10/TGF-DC-stimulated T cell hyporesponsiveness could not be reverted and showed higher percentages of late apoptosis, p<0.02.ConclusionsThe inherent tolerance induction resistance of activated T cells present during the development of autoimmune diseases has delayed the application of tDC as an alternative therapy. This study highlights the 10/TGF-DC feasibility to induce antigen-specific unresponsiveness in autoreactive T cells generated in patients with APS by inducing apoptosis or T cells with regulatory abilities.

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A subset of CD4+ effector memory T cells suppress T cell-mediated immunity to pulmonary viral infection via integrin αvβ8-dependent activation of latent TGFβ

10.26226/morressier.6170a2077c09fc044a97424a ◽

2021 ◽

Author(s):

Craig McEntee

Keyword(s):

T Cells ◽

T Cell ◽

Viral Infection ◽

Memory T Cells ◽

Effector Memory ◽

Cell Mediated Immunity ◽

Effector Memory T Cells

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IL-7 and IL-15 Levels Reflect the Degree of T Cell Depletion during Lymphopenia and Are Associated with an Expansion of Effector Memory T Cells after Pediatric Hematopoietic Stem Cell Transplantation

The Journal of Immunology ◽

10.4049/jimmunol.2001077 ◽

2021 ◽

pp. ji2001077

Author(s):

Katrine Kielsen ◽

Lisa V. E. Oostenbrink ◽

Erik G. J. von Asmuth ◽

Anja M. Jansen-Hoogendijk ◽

Monique M. van Ostaijen-ten Dam ◽

...

Keyword(s):

T Cells ◽

Stem Cell ◽

T Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Memory T Cells ◽

Effector Memory ◽

Hematopoietic Stem ◽

Effector Memory T Cells

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Flt3 ligand augmentation of T cell mitogenesis and expansion of type 1 effector/memory T cells

International Immunopharmacology ◽

10.1016/s1567-5769(02)00035-8 ◽

2002 ◽

Vol 2 (7) ◽

pp. 925-940 ◽

Cited By ~ 9

Author(s):

R Lee Mosley ◽

Prahlad Parajuli ◽

Vladimir Pisarev ◽

Jennifer Chavez ◽

Amy Meeks ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Memory T Cells ◽

Effector Memory ◽

Flt3 Ligand ◽

Effector Memory T Cells

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CD40L+ CD4+ memory T cells migrate in a CD62P-dependent fashion into reactive lymph nodes and license dendritic cells for T cell priming

Journal of Experimental Medicine ◽

10.1084/jem.20081212 ◽

2008 ◽

Vol 205 (11) ◽

pp. 2561-2574 ◽

Cited By ~ 50

Author(s):

Alfonso Martín-Fontecha ◽

Dirk Baumjohann ◽

Greta Guarda ◽

Andrea Reboldi ◽

Miroslav Hons ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

T Cell ◽

Lymph Nodes ◽

Memory T Cells ◽

Effector Memory ◽

High Endothelial Venules ◽

T Cell Priming ◽

Dc Maturation

There is growing evidence that the maturation state of dendritic cells (DCs) is a critical parameter determining the balance between tolerance and immunity. We report that mouse CD4+ effector memory T (TEM) cells, but not naive or central memory T cells, constitutively expressed CD40L at levels sufficient to induce DC maturation in vitro and in vivo in the absence of antigenic stimulation. CD4+ TEM cells were excluded from resting lymph nodes but migrated in a CD62P-dependent fashion into reactive lymph nodes that were induced to express CD62P, in a transient or sustained fashion, on high endothelial venules. Trafficking of CD4+ TEM cells into chronic reactive lymph nodes maintained resident DCs in a mature state and promoted naive T cell responses and experimental autoimmune encephalomyelitis (EAE) to antigens administered in the absence of adjuvants. Antibodies to CD62P, which blocked CD4+ TEM cell migration into reactive lymph nodes, inhibited DC maturation, T cell priming, and induction of EAE. These results show that TEM cells can behave as endogenous adjuvants and suggest a mechanistic link between lymphocyte traffic in lymph nodes and induction of autoimmunity.

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Unique gene expression program of human germinal center T helper cells

Blood ◽

10.1182/blood-2004-03-1206 ◽

2004 ◽

Vol 104 (7) ◽

pp. 1952-1960 ◽

Cited By ~ 185

Author(s):

Chang H. Kim ◽

Hyung W. Lim ◽

Jong R. Kim ◽

Lusijah Rott ◽

Peter Hillsamer ◽

...

Keyword(s):

Gene Expression ◽

T Cells ◽

T Cell ◽

Germinal Center ◽

Memory T Cells ◽

Effector Memory ◽

T Helper ◽

Th Cells ◽

Effector Memory T Cells ◽

Expression Program

Abstract Gene expression profiling was used to compare the gene expression patterns of human germinal center (GC) T helper (Th) cells with other CD4+ T-cell subsets (naive, central, and effector memory T cells). GC-Th cells, specifically localized in germinal centers to help B cells, are distantly related to central and effector memory T cells in global gene expression profiles. GC-Th cells displayed substantial differences in mRNA for adhesion molecules, chemoattractant receptors, and cytokines compared with other populations. Distinct expression of transcriptional factors by GC-Th cells is consistent with the hypothesis that they may be different from other T cells in cell lineage. Interestingly, CXCL13, a critical chemokine for B-cell entry to lymphoid follicles, is one of the most highly up-regulated genes in GC-Th cells. GC-Th cells (but not other T cells) produce and secrete large amounts of functional CXCL13 upon T-cell receptor activation, a process that is dependent on costimulation, requires translation and transcription, and is dramatically enhanced by activation in the presence of GC-B cells. This study revealed for the first time the unique gene expression program of GC-Th cells.

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