A ligand for the chemokine receptor CCR7 can influence the homeostatic proliferation of CD4 T cells and progression of autoimmunity

Homeostasis of T cell numbers in the periphery implies an ability of lympho cytes to sense cell numbers. Although the mechanisms are unknown, we find t hat the chemokine CCL21 (also known as TCA4, SLC, 6Ckine), a ligand for the chemokine receptor CCR7, can regulate homeostasis of CD4 (but not CD8) T c ells. In the absence of CCR7 ligands, transferred CD4 T cells failed to exp and in lymphopenic hosts, whereas in the presence of CCL21 overexpression, homeostatic CD4 T cell proliferation occurred even in nonlymphopenic recipi ents. Ag-specific CD4 T cells transferred into Ag-expressing mice prolifera ted and induced autoimmunity only in lymphopenic recipients. Pancreatic exp ression of CCL21 was sufficient to replace the requirement for lymphopenia in the progression of autoimmune disease. These results suggest that CD4 T cells use local concentrations of CCR7 ligands as an index of T cell steady state numbers and that homeostatic expansion of the T cell population may be a contributing factor in the development of autoimmune disease.