Induced peripheral regulatory T cells: The family grows larger

Höglund, Petter

doi:10.1002/eji.200535797

Cited by 20 publications

(7 citation statements)

References 24 publications

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“…It is interesting that the regulatory T lymphocyte repertoire correlates with the CD4 + T cell expansions. This could reflect induction of a regulatory phenotype in activated T lymphocyte populations, as previously shown [32, 33]. However, overall, there is similar TCR Vβ diversity between population rather than skewing, implying that this T lymphocyte subset is a recently activated T lymphocyte population.…”

Section: Discussionsupporting

confidence: 61%

Flow Cytometric Analysis of TCR Vβ Repertoire in Patients with 22q11.2 Deletion Syndrome

et al. 2011

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In 22q11.2 deletion patients, the normal decrease in T lymphocyte counts after 1–2 years is blunted such that relatively T lymphocyte numbers increase over early childhood, probably via post‐thymic expansion of peripheral lymphocytes. This may leave less T lymphocyte receptor (TCR) diversity than when derived from naive thymic emigrants. We analysed TCR Vβ repertoire on 27 22q11.2 chromosome deletion patients. No patient had infection at sampling. CD3+CD4+ recent thymic emigrants (RTEs) were identified by CD45RA and CD31 expression. TCR Vβ repertoire was determined using four‐colour flow cytometry. Patients and controls showed significant TCR Vβ family usage differences between CD3+CD4+ and CD3+CD4− T lymphocyte subpopulations. Vβ family abnormalities (±3 SD of controls) were identified in 18/27 (67%) patients and 12/47 (25%) controls. In patients, the magnitude of expansions was increased, with some Vβ families representing 37% of the cells present in the subpopulations. There was a significant increase in frequency of abnormalities in CD3+CD4+ (P < 0.001) and CD3+CD4− T lymphocytes (P < 0.05) in patients. A total of 11/16 patients had an abnormal CD4+CD25Bright TCR Vβ repertoire. There was no difference in expansions/contractions between CD4+CD25Bright and CD4+ T lymphocyte repertoires (P = 0.575) for individual patients but significant differences in expansions/contractions between CD4+CD25Bright and CD8+ T lymphocytes repertoires (P = 0.011). There was bias in Vβ usage between CD3+CD4+ and CD3+CD4− T lymphocyte subsets. A total of 67% patients had TCR Vβ repertoire abnormalities, with a trend towards increased repertoire abnormalities with fewer RTEs, suggesting thymic output plays an important role in TCR repertoire diversity. There was no correlation between skewed repertoire and symptoms of infection or autoimmunity.

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Section: Discussionsupporting

confidence: 61%

Flow Cytometric Analysis of TCR Vβ Repertoire in Patients with 22q11.2 Deletion Syndrome

et al. 2011

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“…A variety of other minor Treg subtypes have been recently identified including CD8 ϩ Tregs that appear to limit certain CD4 ϩ T cell effector populations (10). Tregs have also been reported to limit excessive adaptive responses to foreign Ag after infection thereby limiting immunopathology (11,12), although this can result in persistent infection by some infectious agents and/or limit protective responses to acute infection (12)(13)(14)(15).…”

Section: R Egulatory T Cells (Tregs)mentioning

confidence: 99%

T Regulatory Cells Contribute to the Attenuated Primary CD8+ and CD4+ T Cell Responses to Herpes Simplex Virus Type 2 in Neonatal Mice

Fernandez¹,

Puttur

Wang

et al. 2008

The Journal of Immunology

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The first weeks of life are characterized by immune tolerance and increased susceptibility to intracellular pathogens. The neonatal adaptive response to HSV is attenuated compared with adult control models in humans and mice. T Regulatory cells (Tregs) control autoimmunity and excessive immune responses to infection. We therefore compared Treg responses in the draining lymph nodes (LN) of HSV-infected neonatal and adult C57BL/6 mice with the effect of Treg depletion/inactivation by anti-CD25 (PC61) treatment before infection on Ag-specific T cell effector responses at this site. There was a small, but significant increase in the frequency of CD4+Foxp3+ Tregs at day 3 postinfection (p.i.) in the LN of neonatal and adult mice, compared with age-matched mock-infected controls. Depletion of Tregs before HSV infection significantly enhanced HSV-specific CD8+ T cell cytotoxicity in vivo, cell number, activation, and granzyme B expression 4 days p.i. only in neonatal mice, and significantly enhanced CD8+ and CD4+ T cell IFN-γ responses in both infected adults and neonates. Treg depletion also reduced the titer of infectious virus in the draining LN and nervous system of infected neonates on days 2 and 3 p.i. Treg suppression of the neonatal CTL response p.i. with HSV was associated with increased expression of TGF-β in the draining LN at day 4 p.i. compared with uninfected neonates, but IL-10 was increased in infected adults alone. These experiments support the notion that the newborn primary T cell effector responses to HSV are suppressed by Tregs.

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“…FoxP3 acts as a transcriptional repressor of IL‐2 and other cytokine genes including IL‐4 and interferon‐ γ [20, 21]. In addition to the naturally occurring CD4 + CD25 high Treg, several types of induced Treg including Th3 cells and type 1 regulatory (Tr1) T cells have been defined [22, 23].…”

Section: Introductionmentioning

confidence: 99%

An Optimized Method for the Functional Analysis of Human Regulatory T Cells

Oberg¹,

Wesch²,

Lenke³

et al. 2006

Scand J Immunol

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Naturally occurring regulatory T cells (Treg) suppress the activation of antigen‐responsive T cells in a cell contact‐dependent manner. In order to investigate the impact of soluble mediators and receptor–ligand interactions on the interplay between naive T cells and Treg, a reproducible suppressor cell assay which functions in the absence of additional feeder cells or antigen‐presenting cells is mandatory. Here, we describe such a method which is suited to study the modulation of responder T cell/Treg interactions in vitro. Treg were isolated from negatively purified total human CD4+ T cells by positive selection using anti‐CD25 monoclonal antibody (MoAb)‐coated Dynabeads followed by a detachment step. The remaining CD4+ CD25− responder T cells were cocultured with CD4+ CD25+ Treg in the presence of T‐cell Activation/Expansion Beads from Miltenyi Biotec pre‐coated with anti‐CD3 plus anti‐CD28 monoclonal antibody (MoAb). The optimal concentration for coating was 5 μg/ml for both MoAb. At this concentration, strong proliferation of responder T cells was elicited which was almost completely suppressed by Treg at 1:1 cell ratios. When higher concentrations of anti‐CD3/anti‐CD28 MoAb were used for coating, Treg also showed some degree of proliferation. The optimized suppressor assay proved to be highly reproducible and was used here to confirm the partial or complete reversal of Treg‐mediated T‐cell suppression by some cytokines (IL‐2, IL‐15), soluble IL‐6 receptor/IL‐6 fusion protein and recombinant GITR‐ligand. Furthermore, our data confirm that Treg do not need other cell types to suppress proliferation of CD4+ CD25− responder T cells.

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Induced peripheral regulatory T cells: The family grows larger

Cited by 20 publications

References 24 publications

Flow Cytometric Analysis of TCR Vβ Repertoire in Patients with 22q11.2 Deletion Syndrome

Flow Cytometric Analysis of TCR Vβ Repertoire in Patients with 22q11.2 Deletion Syndrome

T Regulatory Cells Contribute to the Attenuated Primary CD8+ and CD4+ T Cell Responses to Herpes Simplex Virus Type 2 in Neonatal Mice

An Optimized Method for the Functional Analysis of Human Regulatory T Cells

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