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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.

Publication ,  Journal Article
Stein, JV; Rot, A; Luo, Y; Narasimhaswamy, M; Nakano, H; Gunn, MD; Matsuzawa, A; Quackenbush, EJ; Dorf, ME; von Andrian, UH
Published in: J Exp Med
January 3, 2000

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 Galpha(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)-1alpha (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 plt/plt 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.

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Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

January 3, 2000

Volume

191

Issue

1

Start / End Page

61 / 76

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Lymphocyte Function-Associated Antigen-1
  • Lymph Nodes
  • Immunology
  • Endothelium, Lymphatic
  • Chemokines, CXC
  • Chemokines, CC
 

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Stein, J. V., Rot, A., Luo, Y., Narasimhaswamy, M., Nakano, H., Gunn, M. D., … von Andrian, U. H. (2000). 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. J Exp Med, 191(1), 61–76. https://doi.org/10.1084/jem.191.1.61
Stein, J. V., A. Rot, Y. Luo, M. Narasimhaswamy, H. Nakano, M. D. Gunn, A. Matsuzawa, E. J. Quackenbush, M. E. Dorf, and U. H. von Andrian. “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.J Exp Med 191, no. 1 (January 3, 2000): 61–76. https://doi.org/10.1084/jem.191.1.61.

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

January 3, 2000

Volume

191

Issue

1

Start / End Page

61 / 76

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Lymphocyte Function-Associated Antigen-1
  • Lymph Nodes
  • Immunology
  • Endothelium, Lymphatic
  • Chemokines, CXC
  • Chemokines, CC