ERK1-deficient mice show normal T cell effector function and are highly susceptible to experimental autoimmune encephalomyelitis.
T cell activation engages multiple intracellular signaling cascades, including the ERK1/2 (p44/p42) pathway. It has been suggested that ERKs integrate TCR signal strength, and are important for thymocyte development and positive selection. However, the requirement of ERKs for the effector functions of peripheral mature T cells and, specifically, for T cell-mediated autoimmunity has not been established. Moreover, the specific requirements for ERK1 vs ERK2 in T cells have not been resolved. Therefore, we investigated the role of ERK1 in T cell immunity to foreign and self Ags and in the induction of experimental autoimmune encephalomyelitis. The results show that in ERK1-deficient (ERK1-/-) mice, the priming, proliferation, and cytokine secretion of T cells to the self Ag myelin oligodendrocyte glycoprotein peptide 35-55 and to the prototypic foreign Ag OVA are not impaired as compared with wild-type mice. Furthermore, ERK1-/- mice are highly susceptible to experimental autoimmune encephalomyelitis induced with myelin oligodendrocyte glycoprotein peptide 35-55. Finally, thymocyte development and mitogen-induced proliferation were not impaired in ERK1-/- mice on the inbred 129 Sv and C57BL/6 backgrounds. Collectively, the data show that ERK1 is not critical for the function of peripheral T cells in the response to self and foreign Ags and in T cell-mediated autoimmunity, and suggest that its loss can be compensated by ERK2.
Nekrasova
Tanya
T
Alzheimer Research Laboratory, Department of Neurosciences, Case Western Reserve University, Cleveland, OH 44106, USA.
Shive
Carey
C
Gao
Yuehua
Y
Kawamura
Kazuyuki
K
Guardia
Rocio
R
Landreth
Gary
G
Forsthuber
Thomas G
TG
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003433:Crosses, Genetic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis / Q000378:metabolism; D008969:Molecular Sequence Data; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000201:enzymology / Q000276:immunology
D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3