Journal article
The Cc Chemokine Thymus-Derived Chemotactic Agent 4 (Tca-4, Secondary Lymphoid Tissue Chemokine, 6ckine, Exodus-2) Triggers Lymphocyte Function–Associated Antigen 1–Mediated Arrest of Rolling T Lymphocytes in Peripheral Lymph Node High Endothelial Venules
The Journal of experimental medicine, Vol.191(1), pp.61-76
01/03/2000
DOI: 10.1084/jem.191.1.61
PMCID: PMC2195804
PMID: 10620605
Abstract
T cell homing to peripheral lymph nodes (PLNs) is defined by a multistep sequence of interactions between lymphocytes and endothelial cells in high endothelial venules (HEVs). After initial tethering and rolling via L-selectin, firm adhesion of T cells requires rapid upregulation of lymphocyte function–associated antigen 1 (LFA-1) adhesiveness by a previously unknown pathway that activates a Gα
i
-linked receptor. Here, we used intravital microscopy of murine PLNs to study the role of thymus-derived chemotactic agent (TCA)-4 (secondary lymphoid tissue chemokine, 6Ckine, Exodus-2) in homing of adoptively transferred T cells from T-GFP mice, a transgenic strain that expresses green fluorescent protein (GFP) selectively in naive T lymphocytes (T
GFP
cells). TCA-4 was constitutively presented on the luminal surface of HEVs, where it was required for LFA-1 activation on rolling T
GFP
cells. Desensitization of the TCA-4 receptor, CC chemokine receptor 7 (CCR7), blocked T
GFP
cell adherence in wild-type HEVs, whereas desensitization to stromal cell–derived factor (SDF)-1α (the ligand for CXC chemokine receptor 4 [CXCR4]) did not affect T
GFP
cell behavior. TCA-4 protein was not detected on the luminal surface of PLN HEVs in
plt/plt
mice, which have a congenital defect in T cell homing to PLNs. Accordingly, T
GFP
cells rolled but did not arrest in
plt/plt
HEVs. When TCA-4 was injected intracutaneously into
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mice, the chemokine entered afferent lymph vessels and accumulated in draining PLNs. 2 h after intracutaneous injection, luminal presentation of TCA-4 was detectable in a subset of HEVs, and LFA-1–mediated T
GFP
cell adhesion was restored in these vessels. We conclude that TCA-4 is both required and sufficient for LFA-1 activation on rolling T cells in PLN HEVs. This study also highlights a hitherto undocumented role for chemokines contained in afferent lymph, which may modulate leukocyte recruitment in draining PLNs.
Details
- Title: Subtitle
- The Cc Chemokine Thymus-Derived Chemotactic Agent 4 (Tca-4, Secondary Lymphoid Tissue Chemokine, 6ckine, Exodus-2) Triggers Lymphocyte Function–Associated Antigen 1–Mediated Arrest of Rolling T Lymphocytes in Peripheral Lymph Node High Endothelial Venules
- Creators
- Jens V. Stein - Harvard Medical SchoolAntal Rot - Novartis Forschungsinstitut, A-1235, Vienna, AustriaYi Luo - Harvard UniversityManjunath Narasimhaswamy - Harvard Medical SchoolHideki Nakano - Toho UniversityMichael D. Gunn - Duke UniversityAkio Matsuzawa - Tokyo University of ScienceElizabeth J. Quackenbush - Harvard Medical SchoolMartin E. Dorf - Harvard UniversityUlrich H. von Andrian - Harvard Medical School
- Resource Type
- Journal article
- Publication Details
- The Journal of experimental medicine, Vol.191(1), pp.61-76
- Publisher
- The Rockefeller University Press
- DOI
- 10.1084/jem.191.1.61
- PMID
- 10620605
- PMCID
- PMC2195804
- ISSN
- 0022-1007
- eISSN
- 1540-9538
- Language
- English
- Date published
- 01/03/2000
- Academic Unit
- Urology
- Record Identifier
- 9984320854502771
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