Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES

Abstract

AN important process in the immune response is the migration of different populations of lymphocytes at the proper time to sites of antigenic challenge. Although several chemoattractants are known for broad classes of lymphocytes, such as T and B cells, the process by which lymphocytes of specific subsets, such as helper, cytotoxic or memory T cells, migrate to the appropriate sites remains obscure. Interleukin-8 is a chemoattractant for T cells and neutrophils and is a member of a superfamily of soluble molecules related by a conserved motif containing four cysteine residues. IL-8 and related molecules, including platelet factor 4, constitute the C-X-C class of the superfamily and a group of cytokines produced by haematopoietic cells^3,4 constitute the RANTES/sis or C-C class^4,5. The roles of most of these molecules are not well known, although murine MIP-lα of the C-C branch is a specific inhibitor of haematopoietic stem cell proliferation⁶ and some members of the C-X-C branch are neutrophil-targeted inflammatory agents^7–10. Here we report that the RANTES protein³ of the C-C class causes the selective migration of human blood monocytes and of T lymphocytes expressing the cell surface antigens CD4 and UCHL1. CD4⁺/UCHL1⁺T cells are thought to be prestimulated or primed helper T cells involved in memory T cell function^11–14. The preferential attraction of T-cell subsets by specific cytokines could in part explain how lymphocytes are targeted, and may provide insight into the workings of T cell memory.