Cutting edge: critical role for CD5 in experimental autoimmune encephalomyelitis: inhibition of engagement reverses disease in mice.
The induction phase of experimental autoimmune encephalomyelitis (EAE) in mice is T cell dependent and coreceptors that regulate T cell activation modulate disease development. We report here that mice lacking CD5, an important modulator of T cell activation, exhibit significantly delayed onset and decreased severity of EAE. The resistance to EAE in CD5(-/-) mice was not due to the inability of T cells to respond efficiently to stimulation with MOG(35-55) but was associated with the presence of elevated frequency of apoptotic activated T cells in spleens and DLN. We also observed a net decrease in peripheral activated CD4(+) T cells in CD5(-/-) spleens and DLN 10 days after immunization. We further show that in vivo blockade of CD5 engagement after induction of EAE by soluble CD5-Fc, a treatment that induces elimination of activated T cells, promoted recovery from EAE. Our studies indicate that CD5 regulates survival of activated T cells and provides a target for treatment of T cell-dependent autoimmune diseases such as multiple sclerosis.
Axtell
Robert C
RC
Department of Medicine, University of Alabama at Birmingham, 35294, USA.
Webb
Matthew S
MS
Barnum
Scott R
SR
Raman
Chander
C
D000818:Animals; D018956:CD5 Antigens / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology*; D008024:Ligands; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology; D013997:Time Factors
D018956:CD5 Antigens; D008024:Ligands; D017346:Protein Serine-Threonine Kinases