CXCR3 is required for migration to dermal inflammation by normal and in vivo activated T cells: differential requirements by CD4 and CD8 memory subsets

Lymphocytes in inflamed tissues express numerous chemokine receptors. The relative importance of these receptors for migration in inflammation is unclear. The role of CXCR3 in T cell subset migration was examined using monoclonal antibodies developed to rat CXCR3. CXCR3 was expressed on sixfold more CD8+ (∼30%) than CD4+ (∼5%) T cells in spleen, lymph nodes and blood, and on ∼10% of CD4+CD45RC– (memory) and ∼50% of CD8+CD45RC+ spleen T cells. After immunization, CXCR3 increased tenfold on CD4+ lymph node lymphoblasts (∼55%), and >90% of inflammatory exudate T cells were CXCR3+. CXCR3+ T cells migrated significantly better than CXCR3– T cells to all dermal inflammatory stimuli tested in vivo, even though these T cells are a minority of the memory T cells. Blocking CXCR3 inhibited recruitment of 60–85% of unstimulated T cells and up to 90% of CD8+CD45RC+ effector T cells, but caused