Local delivery of granulocyte macrophage colony-stimulating factor by retrovirally transduced antigen-specific T cells leads to severe, chronic experimental autoimmune encephalomyelitis in mice.
Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS) that can be induced in susceptible mice by the transfer of autoreactive T cells that recognize myelin basic protein (MBP). The onset and subsequent recovery from disease are associated with distinct patterns of cytokine and chemokine expression within the inflammatory lesions of the CNS. Given the likely importance of the local cytokine milieu in regulating the disease process, it would be preferable to administer cytokines locally to the CNS and reduce systemic delivery in order to evaluate their immunoregulatory roles in EAE. For this purpose, we have used retrovirally transduced T cells from MBP-specific T cell receptor transgenic mice in an attempt to target cytokine delivery to the CNS where MBP is primarily expressed. We have found that T cells expressing granulocyte macrophage colony-stimulating factor (GM-CSF) induce severe, chronic EAE from which mice fail to recover. Our results indicate that increased local GM-CSF expression could play an important role in inducing chronic EAE.
Marusic
Suzana
S
Wyeth Research, Building. G, 1 Burtt Road, Andover MA 01810-5901, USA. smarusic@genetics.com
Miyashiro
Joy S
JS
Douhan
John
J
Konz
Richard F
RF
Xuan
DeJun
D
Pelker
Jeffrey W
JW
Ling
Vincent
V
Leonard
John P
JP
Jacobs
Kenneth A
KA
D000818:Animals; D000941:Antigens / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000276:immunology / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D012190:Retroviridae / Q000235:genetics*; D013601:T-Lymphocytes / Q000502:physiology*; D014161:Transduction, Genetic
D000941:Antigens; D004676:Myelin Basic Protein; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor