The effect of the CC chemokine receptor antagonist Met-RANTES on experimental autoimmune uveitis and oral tolerance.
Lymphocyte trafficking is controlled in part by the actions of chemokines. In rat experimental autoimmune uveitis (EAU) we observed differential therapeutic effects of Met-RANTES, a CCR1/CCR5 receptor antagonist, depending on the retinal antigen peptides inducing the disease and the time of application during the afferent or efferent immune response. CCR1 and/or CCR5 blockade may have inhibitory effects on different phases of the autoimmune response, depending on the antigen specificity of T cells in EAU. In contrast, Met-RANTES enhanced therapeutic oral tolerance independently of orally applied antigen.
Diedrichs-Möhring
Maria
M
Section of Immunobiology, Department of Ophthalmology, Ludwig-Maximilians-University, Mathildenstr. 8, 80336 Munich, Germany. Maria.Diedrichs-Moehring@med.uni-muenchen.de
Nelson
Peter J
PJ
Proudfoot
Amanda E I
AE
Thurau
Stephan R
SR
Wildner
Gerhild
G
D000818:Animals; D019393:Arrestin / Q000737:chemistry / Q000633:toxicity; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000188:drug therapy*; D018946:Chemokine CCL5 / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D019742:Chemokines, CC / Q000037:antagonists & inhibitors*; D016207:Cytokines / Q000378:metabolism; D004347:Drug Interactions; D053331:Ectodysplasins; D005123:Eye / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005136:Eye Proteins / Q000737:chemistry / Q000633:toxicity; D007150:Immunohistochemistry / Q000379:methods; D008565:Membrane Proteins / Q000378:metabolism; D010455:Peptides / Q000633:toxicity; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D012177:Retinol-Binding Proteins / Q000737:chemistry / Q000633:toxicity; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000187:drug effects; D013997:Time Factors; D014605:Uveitis / Q000139:chemically induced / Q000188:drug therapy*; D014611:Vaccination / Q000379:methods; D000099214:Retinol-Binding Proteins, Interstitial
D019393:Arrestin; D018946:Chemokine CCL5; D019742:Chemokines, CC; D016207:Cytokines; D053331:Ectodysplasins; D005136:Eye Proteins; D008565:Membrane Proteins; D010455:Peptides; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C108335:RANTES, Met-