R-Ras Regulates XXXX T Cell Migration and @entity8024 Binding.

@entity7307 @entity19 @entity58787 @entity8024 @entity6232
UNASSIGNED: 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 @entity7307 -binding proteins and its role in T cell trafficking has been investigated in R-Ras null @entity19 ( @entity58787 -/-). An examination of the lymphoid organs of @entity58787 -/- @entity19 revealed a 40% reduction in the cellularity of the peripheral lymph nodes. Morphologically, the high endothelial venules of @entity58787 -/- @entity19 were more disorganized and less mature than those of wild-type @entity19 . Furthermore, CD4+ and CD8+ T cells from @entity58787 -/- @entity19 had approximately 42% lower surface expression of @entity6232 / @entity6232 . These aberrant peripheral lymph node phenotypes were associated with proliferative and trafficking defects in @entity58787 -/- T cells. Furthermore, R-Ras could be activated by the chemokine, CCL21. Indeed, @entity58787 -/- T cells had approximately 14.5% attenuation in binding to @entity8024 upon CCL21 stimulation. Finally, in a graft-versus host disease model, recipient @entity19 that were transfused with @entity58787 -/- T cells showed a significant reduction in disease severity when compared with @entity19 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.
