Origins of CD4+ effector and central memory T cells

Pepper, Marion; Jenkins, Marc K.

doi:10.1038/ni.2038

Cited by 348 publications

(334 citation statements)

References 64 publications

Supporting

Mentioning

315

Contrasting

Unclassified

Order By: Relevance

“…Additionally, we observed a higher percentage of helper (CD4+CD62L−) cells in the children with gastrointestinal bacterial infection than in the children with respiratory bacterial infection; these cells are associated with a Th2-type humoral response [8,33]. In contrast, we observed a higher percentage of cytotoxic cells (CD8+CD28−) in the patients with respiratory bacterial infections; these cells are closely related to a Th1-type cellular immune response [34].…”

Section: Discussioncontrasting

confidence: 50%

“…CD62L is expressed on lymphocytes and is involved in regulating cellular trafficking by binding to its ligands on the vascular endothelium [8][9][10]. CD28 is a costimulatory molecule that binds to its ligand, CD86, on antigen-presenting cells (APCs) and provides the second signal required for T cell activation [11].…”

Section: Introductionmentioning

confidence: 99%

“…CD62L− cells are effector memory cells that migrate towards sites of inflammation and are rapidly stimulated by pathogens to execute effector functions, including the production of cytokines, such as IFN-γ, IL-4 and IL-5. CD62L− cells are particularly abundant in the lung, liver and intestine [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Memory AND effector cells in children with bacterial infections of the gastrointestinal and respiratory tracts

Palacios-Martínez¹,

González-Torres²,

Rodríguez-Cruz³

et al. 2012

OJI

View full text Add to dashboard Cite

Infections in infants and children under five years of age are a public health in México and are one of the major causes of death. Methods In this study, lymphocyte immunophenotyping for CD3+ (T-cells), CD3+CD4+, CD3+CD8+, CD3+CD19+, CD3+CD16/56+, CD45RA+, CD45RO+, CD62L− and CD28− were determined in the whole blood of gastrointestinal and respiratory bacterial infected children, using a fourcolor flow cytometry technique. Results: Our data showed that the percentages and the absolute numbers of monocytes and granulocytes are increased in infected children, when compared to the control group. Similarly, we observed increases in the percentages of B lymphocytes, CD8+ cells, memory T cells (CD4+CD45RO+ and CD8+CD45RO+) and effector lymphocytes (CD4+CD62L− and CD8+CD28−) in infected children compared with the control group. In contrast, naive T cells were decreased in the bacterial infected children relative to the control group. Additionally, we used ELISA assays to identify the pathogen agent in gastrointestinal and respiratory infection.

show abstract

Section: Discussioncontrasting

confidence: 50%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Memory AND effector cells in children with bacterial infections of the gastrointestinal and respiratory tracts

Palacios-Martínez¹,

González-Torres²,

Rodríguez-Cruz³

et al. 2012

OJI

View full text Add to dashboard Cite

show abstract

“…Memory T cells further consist of two types: central-and effector-memory T cells on the basis of their homing and functional capacity. Central-memory T cells express high levels of CD62L and CCR7 and mainly circulate through lymphoid organs and rapidly proliferate after restimulation whereas effector-memory T cells are preferentially distributed within nonlymphoid tissues and rapidly exhibit effector functions after restimulation (13,14). In the CD4 T-cell populations, effector and memory T cells with the capacity of different cytokine secretion are developed, such as T helper 1 (Th1) cells producing IFNγ and Th2 cells producing IL-4/IL-5/IL-9/IL-13 (15,16).…”

mentioning

confidence: 99%

Bach2 maintains T cells in a naive state by suppressing effector memory-related genes

Tsukumo

Unno

Muto

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

132

151

View full text Add to dashboard Cite

The transcriptional repressor BTB and CNC homology 2 (Bach2) is thought to be mainly expressed in B cells with specific functions such as class switch recombination and somatic hypermutation, but its function in T cells is not known. We found equal Bach2 expression in T cells and analyzed its function using Bach2-deficient (−/−) mice. Although T-cell development was normal, numbers of peripheral naive T cells were decreased, which rapidly produced Th2 cytokines after TCR stimulation. Bach2 −/− naive T cells highly expressed genes related to effector-memory T cells such as CCR4, ST-2 and Blimp-1. Enhanced expression of these genes induced Bach2 −/− naive T cells to migrate toward CCR4-ligand and respond to IL33. Forced expression of Bach2 restored the expression of these genes. Using Chromatin Immunoprecipitation (ChIP)-seq analysis, we identified S100 calcium binding protein a, Heme oxigenase 1, and prolyl hydroxylase 3 as Bach2 direct target genes, which are highly expressed in effector-memory T cells. These findings indicate that Bach2 suppresses effector memory-related genes to maintain the naive T-cell state and regulates generation of effector-memory T cells. Kruppel-like factor 2 (KLF2) is one of those TF, which regulates the expression of the sphingosine-1-phosphate receptor-1 (S1pr1) in SP cells (2). S1pr1 is required for the egress of SP cells from the thymus, and thus KLF2-deficient (−/−) SP cells accumulate in the thymus. KLF2 positively regulates S1pr1 expression through direct binding to its promoter. KLF2 −/− mice also develop an unusual population of innate-like CD8 +

show abstract

“…Memory cells form a heterogeneous pool marked by differing phenotypic and functional identities and anatomic locations (2)(3)(4). Differences in the kinetics of contraction and susceptibilities to apoptotic stimuli between naive and memory cells and effectors derived from them have been demonstrated (5)(6)(7)(8); however, underlying mechanisms are not completely understood.…”

mentioning

confidence: 99%

Apoptotic Programs Are Determined during Lineage Commitment of CD4+ T Effectors: Selective Regulation of T Effector-Memory Apoptosis by Inducible Nitric Oxide Synthase

Purushothaman

Marcel

Garg

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

Lineage-committed T effectors generated in response to Ag during the inflammatory phase are destined to die during termination of the immune response. We present evidence to suggest that molecular signatures of lineage commitment are reflected in apoptotic cascades activated in CD4+ T effectors. Exemplifying this, ablation of inducible NO synthase (iNOS) protected effector-memory T (TEM) cells, but not TNaive or central-memory T cells, activated in vitro, from apoptosis triggered by cytokine deprivation. Furthermore, attrition of T effectors generated in the secondary, but not the primary, response to Ag was substantially reduced in mice, which received iNOS inhibitors. Distinct patterns of iNOS expression were revealed in wild-type TEM effectors undergoing apoptosis, and ablation of iNOS protein in primary and TEM wild-type effectors confirmed observations made in iNOS−/− cells. Describing molecular correlates of this dependence, mitochondrial damage, activation of the protein Bax, and release from mitochondria of the apoptosis-inducing factor were selectively abrogated in iNOS−/− TEM effectors. Suggesting that iNOS dependence was linked to the functional identity of T cell subsets, both iNOS induction and apoptosis were compromised in IFN-γ−/− TEM effectors, which mirrored the response patterns of iNOS−/− TEM. Collectively, these observations suggest that programs regulating deletion and differentiation are closely integrated and likely encoded during lineage commitment of T effectors.

show abstract

Origins of CD4+ effector and central memory T cells

Cited by 348 publications

References 64 publications

Memory AND effector cells in children with bacterial infections of the gastrointestinal and respiratory tracts

Memory AND effector cells in children with bacterial infections of the gastrointestinal and respiratory tracts

Bach2 maintains T cells in a naive state by suppressing effector memory-related genes

Apoptotic Programs Are Determined during Lineage Commitment of CD4+ T Effectors: Selective Regulation of T Effector-Memory Apoptosis by Inducible Nitric Oxide Synthase

Contact Info

Product

Resources

About