Cd25+cd4+ Regulatory T Cell Migration Requires L-selectin Expression: L-selectin Transcriptional Regulation Balances Constitutive Receptor Turnover.
From: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Jan 2007
- ISSN: 0022-1767
- Volume: 178
- Issue: 1
- Pages: 291-300
- Medium: Print
- Language: English
- Citation (JAMA): Venturi Guglielmo M, Conway Rochelle M, Steeber Douglas A, et al. Cd25+cd4+ Regulatory T Cell Migration Requires L-selectin Expression: L-selectin Transcriptional Regulation Balances Constitutive Receptor Turnover.. J. Immunol. Jan 2007;178:291-300
Abstract
The molecular mechanisms controlling regulatory CD25(+)Foxp3(+)CD4(+) T cell (T(reg)) migration are central to in vivo immune responses. T(reg) cell subsets differentially express L-selectin, an adhesion molecule mediating lymphocyte migration to peripheral LNs (PLNs) and leukocyte rolling during inflammation. In this study, L-selectin was essential for T(reg) cell migration and normal tissue distribution. Specifically, there was a 90% reduction in PLN T(reg) cells in L-selectin(-/-) mice with a compensatory increase in spleen T(reg) cell numbers. Unexpectedly, however, 40% of the CD4(+) T cells remaining within PLNs of L-selectin(-/-) mice were T(reg) cells. The migratory properties of T(reg) cells were nonetheless markedly different from those of naive CD4(+) T cells, with 3- to 9-fold lower migration of T(reg) cells into PLNs and approximately 2-fold lower migration into the spleen. T(reg) cells also turned over cell surface L-selectin at a faster rate than CD25(-)CD4(+) T cells, but maintained physiologically appropriate L-selectin densities for optimal migration. Specifically, T(reg) cells expressed 30-40% more cell surface L-selectin when its endoproteolytic cleavage was blocked genetically, which resulted in a 2-fold increase in T(reg) cell migration into PLNs. However, increased L-selectin cleavage by T(reg) cells in wild-type mice was accompanied by 2-fold higher L-selectin mRNA levels, which resulted in equivalent cell surface L-selectin densities on T(reg) and naive T cells. Thus, T(reg) cells and CD25(-)CD4(+) T cells share similar requirements for L-selectin expression during migration, although additional molecular mechanisms constrain T(reg) cell migration beyond what is required for naive CD4(+) T cell migration.
Mesh Headings (Keywords): Animals, Antigens, CD, Antigens, CD4, Cell Movement, Gene Expression Regulation, Integrin alpha Chains, Interleukin-2 Receptor alpha Subunit, L-Selectin, Lymph Nodes, Lymphocyte Activation, Mice, Mice, Mutant Strains, Receptors, Immunologic, T-Lymphocytes, Regulatory, Transcription, Genetic
Check for Full Text / PubMed Unique Identifier (PMID): 17182566
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.