Experimental autoimmune encephalomyelitis develops in CC chemokine receptor 7-deficient mice with altered T-cell responses.
CC chemokine receptor 7 (CCR7) is involved in the initiation of immune responses by mediating the migration of naïve T cells and mature dendritic cells to T-cell-rich zones of secondary lymphoid organs where antigen presentation occurs. To address whether CCR7 plays a role in the development of autoimmunity, we induced experimental autoimmune encephalomyelitis in CCR7-deficient mice on a C57BL/6 background (CCR7(-/-)) using the neuroantigen, myelin oligodendrocyte glycoprotein 35-55 amino acid peptide (MOG((35-55))) and Bordetella pertussis toxin (PTX). CCR7(-/-) mice acquired disease with an intensity similar to wild-type littermates. MOG((35-55))-specific lymphocyte responses were dominant in the spleen of CCR7(-/-) mice, rather than in lymph nodes as observed in wild-type mice. These results indicate that effective immune responses (with altered kinetics) can develop in the absence of CCR7 but develop in the spleen rather than lymph nodes as CCR7 is necessary for T and dendritic cells to enter lymph nodes.
Pahuja
A
A
Departmen of Discovery Biology, Neurocrine Biosciences, Inc., San Diego, CA 92130, USA.
Maki
R A
RA
Hevezi
P A
PA
Chen
A
A
Verge
G M
GM
Lechner
S M
SM
Roth
R B
RB
Zlotnik
A
A
Alleva
D G
DG
D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000378:metabolism; D002908:Chronic Disease; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D005260:Female; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
C515371:Ccr7 protein, mouse; D019742:Chemokines, CC; D054400:Receptors, CCR7; D019707:Receptors, Chemokine