Chemokines and chemokine receptors in multiple sclerosis

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DESCRIPTION (adapted from page 125). The project will study chemokine receptors on T cells and mononuclear phagocytes (blood-borne monocytes, macrophages, microglia) in a set of related tissues: Blood and CSF from MS patients, and blood and brains from marmosets with autoimmune disease. The stated hypothesis is that "chemokine receptors are significantly involved in leukocyte invasion, differentiation and activation in the CNS during MS." "Functional significance" will be studied by "quantitating receptor-bearing cells." It is expected that the work will "define molecular targets for therapy." (pg. 125, first par.) Aim 1 defines chemokine receptors on T cells in MS brain. The hypothesis is that T cells in MS lesions representing different stages of disease activity or patterns of demyelination will show different chemokine receptor profiles. The receptors to be studied are CXCR3 and CCR5, characteristic of Th1 cells; CCR4 and CCR3, characteristic of Th2 cells; and CXCR4, expressed by naive T cells. The PI will also ask which cells express IP-10 and RANTES, which are ligands for the Th1 receptors. Aim 2 performs a similar analysis for mononuclear phagocytes in MS brain, to test a similar hypothesis. The receptors to be studied are CCR2, characteristic of monocytes; CCR1, characteristic of macrophages; and CCR5, characteristic of phagocytic macrophages and activated microglia. Aim 3 defines the same receptors on cells from blood and CSF of MS patients (3a), and blood and brain from marmosets (3b). It is explained that AIM 3 "examines the functional significance of receptor expression (p. 125, last 3 lines)."