CD25+Foxp3+ Regulatory T Cells Facilitate CD4+ T Cell Clonal Anergy Induction during the Recovery from Lymphopenia

Vanasek, Tracy L.; Nandiwada, Sarada L.; Jenkins, Marc K.; Mueller, Daniel L.

doi:10.4049/jimmunol.176.10.5880

Cited by 23 publications

(21 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was recently shown that CD4 ϩ CD25 ϩ Tregs prevent autoimmune gastritis in lymphopenic mice by limiting the ability of adoptively transferred naive gastric parietal cell-specific CD4 cells to differentiate into IFN-␥-expressing Th1 effectors, even when an excess of nonregulatory T cells are added to reduce lymphopenia-induced proliferation (44). It has also been reported that Tregs facilitate the development of CD4 cell anergy during the recovery from lymphopenia (45). Tregs might therefore be more critical for programming CD4 cell tolerization under lymphopenic or partially lymphopenic conditions than during steady state conditions.…”

Section: Discussionmentioning

confidence: 99%

Steady State Dendritic Cells Present Parenchymal Self-Antigen and Contribute to, but Are Not Essential for, Tolerization of Naive and Th1 Effector CD4 Cells

Hagymasi

Slaiby

Mihalyo

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

Bone marrow-derived APC are critical for both priming effector/memory T cell responses to pathogens and inducing peripheral tolerance in self-reactive T cells. In particular, dendritic cells (DC) can acquire peripheral self-Ags under steady state conditions and are thought to present them to cognate T cells in a default tolerogenic manner, whereas exposure to pathogen-associated inflammatory mediators during the acquisition of pathogen-derived Ags appears to reprogram DCs to prime effector and memory T cell function. Recent studies have confirmed the critical role of DCs in priming CD8 cell effector responses to certain pathogens, although the necessity of steady state DCs in programming T cell tolerance to peripheral self-Ags has not been directly tested. In the current study, the role of steady state DCs in programming self-reactive CD4 cell peripheral tolerance was assessed by combining the CD11c-diphtheria toxin receptor transgenic system, in which DC can be depleted via treatment with diphtheria toxin, with a TCR-transgenic adoptive transfer system in which either naive or Th1 effector CD4 cells are induced to undergo tolerization after exposure to cognate parenchymally derived self-Ag. Although steady state DCs present parenchymal self-Ag and contribute to the tolerization of cognate naive and Th1 effector CD4 cells, they are not essential, indicating the involvement of a non-DC tolerogenic APC population(s). Tolerogenic APCs, however, do not require the cooperation of CD4+CD25+ regulatory T cells. Similarly, DC were required for maximal priming of naive CD4 cells to vaccinia viral-Ag, but priming could still occur in the absence of DC.

show abstract

Section: Discussionmentioning

confidence: 99%

Steady State Dendritic Cells Present Parenchymal Self-Antigen and Contribute to, but Are Not Essential for, Tolerization of Naive and Th1 Effector CD4 Cells

Hagymasi

Slaiby

Mihalyo

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Their tolerogenic activity has been attributed primarily to the profound T cell depletion from the circulating pool via complement-dependent lysis or Fas/Fas ligand-mediated apoptosis (36,37), although emerging evidence suggests also a role for Treg expansion during lymphopenia-induced homeostatic proliferation (6,26,38,39 ϩ CD25 high cells that were taken from these patients did not express the CD69 activation marker but high levels of the Treg hallmark FOXP3. Moreover, they were hyporesponsive to alloantigens and capable of suppressing the alloreactive immune response of autologous effector CD25 Ϫ/low T cells against donor antigens in co-cultures.…”

Section: Discussionmentioning

confidence: 99%

“…Experimental evidence exists that Treg expand after lymphopenia that is induced by T cell-depleting agents (5)(6)(7). Recently, the humanized anti-CD52 mAb Campath-1H (Alemtuzumab; Schering Plough, Milan, Italy) was used to reduce markedly both circulating and bone marrow lymphocytes for several months in kidney transplant recipients (8).…”

mentioning

confidence: 99%

Regulatory T Cells and T Cell Depletion

Noris¹,

Casiraghi²,

Todeschini³

et al. 2007

Journal of the American Society of Nephrology

212

170

View full text Add to dashboard Cite

؉ CD25 high cells that expressed FOXP3 underwent homeostatic peripheral expansion during immune reconstitution, more intense in patients who received sirolimus than in those who were given CsA. T cells that were isolated from peripheral blood long term after transplantation were hyporesponsive to alloantigens in both groups. In sirolimus-but not CsA-treated patients, hyporesponsiveness was reversed by Treg depletion. T cells from CsA-treated patients were anergic. Thus, lymphopenia and calcineurin-dependent signaling seem to be primary mediators of CD4 ؉ CD25 high Treg expansion in renal transplant patients. These findings will be instrumental in developing "tolerance permissive" immunosuppressive regimens in the clinical setting.

show abstract

“…Our kinetic analyses of circulating lymphocyte count in patients with DIHS showed that a lymphopenic state immediately preceded lymphocytosis, a finding typically seen at the onset of DIHS, and that Treg cells were expanded during the recovery from lymphopenia, coincident with the onset (data not shown). Indeed, reconstitution of T cell-deficient mice by an adoptive transfer of mature peripheral lymphocytes was accompanied by rapid expansions of Treg cells that facilitated CD4 ϩ T cell clonal anergy induction probably to prevent the development of overt autoimmunity in hosts recovering from lymphopenia (45).…”

Section: Discussionmentioning

confidence: 99%

Defective Regulatory T Cells In Patients with Severe Drug Eruptions: Timing of the Dysfunction Is Associated with the Pathological Phenotype and Outcome

Takahashi

Kano

Yamazaki

et al. 2009

The Journal of Immunology

237

200

View full text Add to dashboard Cite

Toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DIHS) represent two ends of a spectrum of severe drug eruptions: DIHS is unique in that severe epidermal damage seen in TEN is absent, sequential reactivations of herpesviruses occur, and autoimmunity often ensues. To investigate whether changes in regulatory T (Treg) cell function would contribute to variability in the clinical manifestations, we examined the frequency, phenotype, and function of Treg cells both during the acute stage and again long after clinical resolution of both diseases. Dramatic expansions of functional Treg cells were found in the acute stage of DIHS. In contrast, Treg function was profoundly impaired in TEN, although present in normal frequency. Skin homing addressins were more preferentially expressed on Treg cells in DIHS than in TEN. Indeed, Treg cells were more abundantly present in the skin lesions of DIHS. Surprisingly, Treg cells contracted upon resolution of DIHS became functionally deficient, whereas their functional defects in TEN were restored upon recovery. These findings indicate that a transitory impairment in their function during the acute stage of TEN may be related to severe epidermal damage, while a gradual loss of their function after resolution of DIHS may increase the risk of subsequently developing autoimmune disease.

show abstract

CD25+Foxp3+ Regulatory T Cells Facilitate CD4+ T Cell Clonal Anergy Induction during the Recovery from Lymphopenia

Cited by 23 publications

References 52 publications

Steady State Dendritic Cells Present Parenchymal Self-Antigen and Contribute to, but Are Not Essential for, Tolerization of Naive and Th1 Effector CD4 Cells

Steady State Dendritic Cells Present Parenchymal Self-Antigen and Contribute to, but Are Not Essential for, Tolerization of Naive and Th1 Effector CD4 Cells

Regulatory T Cells and T Cell Depletion

Defective Regulatory T Cells In Patients with Severe Drug Eruptions: Timing of the Dysfunction Is Associated with the Pathological Phenotype and Outcome

Contact Info

Product

Resources

About