Homing of immature thymocytes to the subcapsular microenvironment within the thymus is not an absolute requirement for T cell development

Benz, Claudia; Heinzel, Kornelia; Bleul, Conrad C.

doi:10.1002/eji.200425248

Cited by 106 publications

(113 citation statements)

References 34 publications

(52 reference statements)

Supporting

Mentioning

104

Contrasting

Unclassified

Order By: Relevance

“…Our data show that FoxP3 ϩ thymocytes undergo a developmental switch in trafficking receptor expression from CXCR4 medium CCR9 high CCR8 high CCR7 low (DN FoxP3 Ϫ cells) to CXCR4 high CCR9 high CCR8 low CCR7 low (DP FoxP3 ϩ cells), and finally to CXCR4 low CCR9 low CCR8 low CCR7 high (mature SP FoxP3 ϩ cells). The CCR9 ligand CCL25 is expressed by thymic epithelial cells and dendritic cells (50,51), and provides the signal important for their localization in the subcapsular region of the thymus (44,52). The major CCR8 ligand CCL1 is expressed by thymic macrophages and fibrous septa epithelial cells (53).…”

Section: Discussionmentioning

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

112

128

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

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

112

128

View full text Add to dashboard Cite

show abstract

“…Ⅺ, Correspond to the thymidine kinase expression cassette (tk), to the loxP-flanked neomycin gene, and to the pBluescript IIKS ϩ vector (pBS) (3). Structure of the targeted allele following homologous recombination (4). Final structure of the targeted allele after removal of the neomycin-resistance gene via Cre-mediated recombination with Cre Deleter mice.…”

Section: Generation Of Ccl25-deficient Micementioning

confidence: 99%

Impaired Accumulation of Antigen-Specific CD8 Lymphocytes in Chemokine CCL25-Deficient Intestinal Epithelium and Lamina Propria

Wurbel

Malissen

Guy‐Grand

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

CCL25 and CCR9 constitute a chemokine/receptor pair involved in T cell development and in gut-associated immune responses. In this study, we generated CCL25−/− mice to answer questions that could not be addressed with existing CCR9−/− mice. Similar phenotypes were observed for both CCL25−/− and CCR9−/− mice, consistent with the notion that CCL25 and CCR9 interact with each other exclusively. We assessed the requirement for CCL25 in generating CCR9high CD8 intestinal memory-phenotype T cells and the subsequent accumulation of these cells within effector sites. TCR-transgenic naive CD8 T cells were transferred into wild-type or CCL25-deficient hosts. Oral sensitization with Ag allowed these naive donor cells to efficiently differentiate into CCR9high memory-phenotype cells within the mesenteric lymph nodes of wild-type hosts. This differentiation event occurred with equal efficiency in the MLN of CCL25-deficient hosts, demonstrating that CCL25 is not required to induce the CCR9high memory phenotype in vivo. However, we found that CCL25 deficiency severely impaired the Ag-dependent accumulation of donor-derived CD8 T cells within both lamina propria and epithelium of the small intestine. Thus, although CCL25 is not necessary for generating memory-phenotype CD8 T cells with “gut-homing” properties, this chemokine is indispensable for their trafficking to the small intestine.

show abstract

“…In fact, Benz et al [19] have recently identified a migratory event occurring at the DN3 stage that may require CCR9 function. This group compared thymic sections from WT and CCR9-deficient mice.…”

Section: Induction Of Ccr9 Expression At the Dn3 Stagementioning

confidence: 99%

“…Benz et al [19] speculated that perhaps CCR9 is necessary for CD25 + thymocytes to home to the SCZ. However, our current findings suggest an alternative scenario: We propose that CCR9 actually helps thymocytes to escape from the SCZ, to continue their further development.…”

Section: Induction Of Ccr9 Expression At the Dn3 Stagementioning

confidence: 99%

Complex regulation of CCR9 at multiple discrete stages of T cell development

2005

View full text Add to dashboard Cite

We have conducted a comprehensive assessment of CCR9 expression and function at the important milestone stages of murine thymocyte development. We reveal an unusually complex regulatory pattern, in which CCR9 influences T cell development at several widely dispersed stages. We find that CCR9 is not expressed within the thymus until the double-negative (DN)3 stage, although it appears to contribute to T cell precursor development prior to residence in the thymus. CCR9 expression is influenced by pre-T cell receptor signals, and is dramatically up-regulated in a population that appears to be transitional between the DN4 and double-positive stages. In the periphery, functional CCR9 is expressed by all naive CD8 T cells, but not by naive CD4 T cells. To our knowledge, this latter finding is the first difference observed in homing receptor expression between naive lymphocyte populations. This suggests that naive CD8 T cells might have access to lymphoid microenvironments from which naive CD4 T cells are excluded.

show abstract

Homing of immature thymocytes to the subcapsular microenvironment within the thymus is not an absolute requirement for T cell development

Cited by 106 publications

References 34 publications

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

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

Impaired Accumulation of Antigen-Specific CD8 Lymphocytes in Chemokine CCL25-Deficient Intestinal Epithelium and Lamina Propria

Complex regulation of CCR9 at multiple discrete stages of T cell development

Contact Info

Product

Resources

About