R-Ras Regulates Murine T Cell Migration and Intercellular Adhesion Molecule-1 Binding

PLoS One. 2015 Dec 28;10(12):e0145218. doi: 10.1371/journal.pone.0145218. eCollection 2015.

Abstract

The trafficking of T-lymphocytes to peripheral draining lymph nodes is crucial for mounting an adaptive immune response. The role of chemokines in the activation of integrins via Ras-related small GTPases has been well established. R-Ras is a member of the Ras-subfamily of small guanosine-5'-triphosphate-binding proteins and its role in T cell trafficking has been investigated in R-Ras null mice (Rras-/-). An examination of the lymphoid organs of Rras-/- mice revealed a 40% reduction in the cellularity of the peripheral lymph nodes. Morphologically, the high endothelial venules of Rras-/- mice were more disorganized and less mature than those of wild-type mice. Furthermore, CD4+ and CD8+ T cells from Rras-/- mice had approximately 42% lower surface expression of L-selectin/CD62L. These aberrant peripheral lymph node phenotypes were associated with proliferative and trafficking defects in Rras-/- T cells. Furthermore, R-Ras could be activated by the chemokine, CCL21. Indeed, Rras-/- T cells had approximately 14.5% attenuation in binding to intercellular adhesion molecule 1 upon CCL21 stimulation. Finally, in a graft-versus host disease model, recipient mice that were transfused with Rras-/- T cells showed a significant reduction in disease severity when compared with mice transplanted with wild-type T cells. These findings implicate a role for R-Ras in T cell trafficking in the high endothelial venules during an effective immune response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion / immunology
  • Cell Movement / genetics
  • Cell Movement / physiology*
  • Cell Proliferation
  • Chemokine CCL21 / metabolism
  • Enzyme Activation
  • Female
  • Graft vs Host Disease / immunology*
  • Intercellular Adhesion Molecule-1 / metabolism*
  • L-Selectin / biosynthesis
  • L-Selectin / metabolism
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Lymphocyte Function-Associated Antigen-1 / biosynthesis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Binding
  • Spleen / cytology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / transplantation
  • ras Proteins / genetics
  • ras Proteins / metabolism*

Substances

  • Chemokine CCL21
  • Lymphocyte Function-Associated Antigen-1
  • Intercellular Adhesion Molecule-1
  • L-Selectin
  • Rras protein, mouse
  • ras Proteins