title: R-Ras Regulates Murine T Cell Migration and Intercellular Adhesion Molecule-1 Binding.
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.
authors.affiliation: Department of Pediatrics, The Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Xiaocai
authors.initials: X
authors.lastname: Yan
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR.
authors.forename: Mingfei
authors.initials: M
authors.lastname: Yan
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Yihe
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Oncological Sciences, The Mount Sinai School of Medicine, New York, New York, United States of America.
authors.forename: Gobind
authors.initials: G
authors.lastname: Singh
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Mei
authors.initials: M
authors.lastname: Yu
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Demin
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, The Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.|Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Hillery
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Chan
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D054421:Chemokine CCL21 / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D019041:L-Selectin / Q000096:biosynthesis / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000378:metabolism* / Q000637:transplantation; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D054421:Chemokine CCL21; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; C513254:Rras protein, mouse; D018631:ras Proteins