Skin‐homing CLA<sup>+</sup>T cells and regulatory CD25<sup>+</sup>T cells represent major subsets of human peripheral blood memory T cells migrating in response to CCL1/I‐309

Colantonio, Lucia; Iellem, Andrea; Sinigaglia, Francesco; D’Ambrosio, Daniele

doi:10.1002/1521-4141(200212)32:12<3506::aid-immu3506>3.0.co;2-#

Cited by 87 publications

(66 citation statements)

References 37 publications

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“…by use of the marker a E (CD103), into a lineage or differentiation stage of natural, naive-like a E -CD25 + Treg and into that of a E + Treg (either CD25 + or CD25 -) with the phenotype of effector/memory cells [3], a distinction that might partially relate to the differentiation into natural and adaptive Treg [4]. Whereas naive-like Treg express molecules including CD62L and CC chemokine receptor 7 (CCR7), allowing recirculation through lymphoid tissues [3,5,6], effector/memory-like Treg display a high chemokine and homing receptor versatility and efficiently migrate into peripheral tissues and inflamed sites [3,5,[7][8][9][10][11][12]. These findings prompted us to propose a model of division of labor that is largely based on the differential migration behavior of naiveand effector/memory-like Treg subsets [2,3].…”

Section: Introductionmentioning

confidence: 99%

Distinctive role of CCR7 in migration and functional activity of naive‐ and effector/memory‐like Treg subsets

et al. 2007

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Foxp3 + CD25 + CD4 + Treg play a fundamental role in the maintenance of self tolerance and the control of inflammatory reactions. Previous data demonstrated a division of labor between naive-and effector/memory-like Treg subsets, which is largely based on their lymph node-recirculating and inflammation-seeking migration behavior, respectively. The chemokine receptor CCR7 is expressed on both types of Treg subsets, albeit at different levels. Whether it fulfills similar or distinct roles in these subsets has not been studied so far. We here show that the recirculation of naive-like Treg through LN and, to some extent, the gut is dependent on CCR7. Lack of CCR7 not only prevents recirculation, but also almost completely abolishes the ability of naive-like Treg to control the priming phase of an immune response. In contrast, CCR7 deficiency in effector/memory-like Treg promotes their accumulation in inflamed sites, compatible with a role of CCR7 for exit from the tissue. Local Treg accumulation was accompanied by an enhanced suppression of inflammation. Together, our findings provide conclusive evidence that CCR7 expression on Treg differentially controls in vivo function of the naive-and effector/memory-like subsets.

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Section: Introductionmentioning

confidence: 99%

Distinctive role of CCR7 in migration and functional activity of naive‐ and effector/memory‐like Treg subsets

et al. 2007

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Section: Introductionmentioning

confidence: 99%

“…Treg are by no means homogeneous, but rather can be subdivided into naïve-like subsets, which preferentially recirculate through lymphoid tissues, and effector/memory subsets, which efficiently migrate into peripheral sites and sites of ongoing immune responses [30][31][32][33]. Thus, it is not surprising that Treg display a high HR versatility [31,[34][35][36][37][38][39].A few studies have demonstrated the capacity of Treg to down-regulate established immune reactions [31,[40][41][42], and, therefore, it has been suggested that regulation might act locally in the inflammatory environment. Indeed, we and others have recently demonstrated that expression of certain HR such as selectin ligands and chemokine receptors on Treg subsets critically influences their suppressive capacity in vivo [43][44][45][46], suggesting that appropriate localization is indispensable for Treg function [30].…”

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confidence: 99%

Induction of organ‐selective CD4⁺ regulatory T cell homing

et al. 2007

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Compelling evidence suggests that Foxp3 + CD25 + CD4 + Treg play a fundamental role in immunoregulation. We have previously demonstrated that Treg have to enter peripheral tissues to suppress ongoing inflammation. However, relatively little is known about how Treg acquire the expression of homing receptors required for tissue-or inflammationspecific migration. Migratory properties of conventional naïve T cells are shaped by the tissue microenvironment and organ-specific dendritic cells during priming. Here, we show that this basic concept also holds true for CD25 + CD4 + Treg: Priming of Treg within peripheral LN led to the expression of selectin ligands, which facilitate migration into inflamed skin, whereas activation within mesenteric LN led to induction of the integrin a 4 b 7 , which is required for migration into mucosal tissues. Furthermore, we could establish in vitro culture systems containing either dendritic cells from mesenteric and peripheral LN, or retinoic acid and IL-12 as polarizing compounds to induce mucosa-and skin-seeking Treg, respectively. Together, our results demonstrate that Treg, similarly to conventional T cells, can be configured with organ-selective homing properties allowing efficient targeting into distinct tissues. IntroductionMigration of T cell subsets to different tissues is determined by the combined expression of adhesion molecules and chemokine receptors (CCR) on the cell surfaces [1][2][3][4]. Among these homing receptors (HR), the integrin a 4 b 7 [5,6] and the chemokine receptor CCR9 [7][8][9] mediate the homing of T cell subsets to GALT such as mesenteric LN (mLN) and Peyer's patches (PP) and to the small intestinal lamina propria and the mucosal epithelium. In contrast, T cell trafficking to the skin is mediated by P-(P-lig) and E-(E-lig) selectin ligands [10,11] as well as .Recently, a number of studies have described that antigen-dependent differentiation of naïve T cells in lymphoid organs leads to the generation of effector T cells exhibiting a capacity to enter peripheral extralymphoid tissues [2]. Effector T cells generated in different lymphoid organs display distinct tissue tropism, which is regulated by an organ-specific induction of adhesion molecules and chemokine receptors during T cell priming [4,[15][16][17][18][19][20][21]. For example, T cells activated in mLN and PP draining the gut acquire high levels of the integrin a 4 b 7 , whereas activation in skin-draining peripheral LN (pLN) results in the upregulation of selectin ligands such as P-lig. Tissuespecific DC have been shown in a number of in vitro and in vivo studies to be involved in the instruction of naïve T cells [4,[17][18][19][20][22][23][24] reported that GALT DC were capable of converting metabolites of dietary vitamin A into retinoic acid (RA), which in turn induced T cell expression of a 4 b 7 and CCR9, leading to the generation of gut-tropic T cells. However, the factors, which are involved in the generation of skin-specific T cell homing in vivo, are largely unknown, although important ...

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“…It has been reported that CD4 ϩ CD25 ϩ or FoxP3 ϩ Tregs express CCR4, CCR5, CCR7, CCR8, CCR10, CXCR4, and CXCR5 and L-selectin, E-selectin, and P-selectin ligands (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). CD103 ϩ Tregs express effector/memory-type trafficking receptors, and CD103 Ϫ Tregs express lymphoid tissue homing receptors (20).…”

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confidence: 99%

FoxP3+ T Cells Undergo Conventional First Switch to Lymphoid Tissue Homing Receptors in Thymus but Accelerated Second Switch to Nonlymphoid Tissue Homing Receptors in Secondary Lymphoid Tissues

Lee

Kang

Kim

2007

The Journal of Immunology

113

128

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Forkhead box P3 (FoxP3)-positive T cells are a specialized T cell subset for immune regulation and tolerance. We investigated the trafficking receptor switches of FoxP3+ T cells in thymus and secondary lymphoid tissues and the functional consequences of these switches in migration. We found that FoxP3+ T cells undergo two discrete developmental switches in trafficking receptors to migrate from primary to secondary and then to nonlymphoid tissues in a manner similar to conventional CD4+ T cells as well as unique to the FoxP3+ cell lineage. In the thymus, precursors of FoxP3+ cells undergo the first trafficking receptor switch (CCR8/CCR9→CXCR4→CCR7), generating mostly homogeneous CD62L+CCR7+CXCR4lowFoxP3+ T cells. CXCR4 expression is regained in FoxP3+ thymic emigrants in the periphery. Consistent with this switch, recent FoxP3+ thymic emigrants migrate exclusively to secondary lymphoid tissues but poorly to nonlymphoid tissues. The FoxP3+ thymic emigrants undergo the second switch in trafficking receptors for migration to nonlymphoid tissues upon Ag priming. This second switch involves down-regulation of CCR7 and CXCR4 but up-regulation of a number of memory/effector type homing receptors, resulting in generation of heterogeneous FoxP3+ T cell subsets expressing various combinations of trafficking receptors including CCR2, CCR4, CCR6, CCR8, and CCR9. A notable difference between the FoxP3+ and FoxP3− T cell populations is that FoxP3+ T cells undergo the second homing receptor switch at a highly accelerated rate compared with FoxP3− T cells, generating FoxP3+ T cells with unconventionally efficient migratory capacity to major nonlymphoid tissues.

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Skin‐homing CLA⁺T cells and regulatory CD25⁺T cells represent major subsets of human peripheral blood memory T cells migrating in response to CCL1/I‐309

Cited by 87 publications

References 37 publications

Distinctive role of CCR7 in migration and functional activity of naive‐ and effector/memory‐like Treg subsets

Distinctive role of CCR7 in migration and functional activity of naive‐ and effector/memory‐like Treg subsets

Induction of organ‐selective CD4⁺ regulatory T cell homing

FoxP3+ T Cells Undergo Conventional First Switch to Lymphoid Tissue Homing Receptors in Thymus but Accelerated Second Switch to Nonlymphoid Tissue Homing Receptors in Secondary Lymphoid Tissues

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Skin‐homing CLA+T cells and regulatory CD25+T cells represent major subsets of human peripheral blood memory T cells migrating in response to CCL1/I‐309

Cited by 87 publications

References 37 publications

Distinctive role of CCR7 in migration and functional activity of naive‐ and effector/memory‐like Treg subsets

Distinctive role of CCR7 in migration and functional activity of naive‐ and effector/memory‐like Treg subsets

Induction of organ‐selective CD4+ regulatory T cell homing

FoxP3+ T Cells Undergo Conventional First Switch to Lymphoid Tissue Homing Receptors in Thymus but Accelerated Second Switch to Nonlymphoid Tissue Homing Receptors in Secondary Lymphoid Tissues

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Skin‐homing CLA⁺T cells and regulatory CD25⁺T cells represent major subsets of human peripheral blood memory T cells migrating in response to CCL1/I‐309

Induction of organ‐selective CD4⁺ regulatory T cell homing