Abstract
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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Cell Differentiation / genetics
-
Cell Differentiation / immunology
-
Cells, Cultured
-
Crosses, Genetic
-
Encephalomyelitis, Autoimmune, Experimental / enzymology
-
Encephalomyelitis, Autoimmune, Experimental / genetics
-
Encephalomyelitis, Autoimmune, Experimental / immunology
-
Female
-
Genetic Predisposition to Disease
-
Glycoproteins / administration & dosage
-
Glycoproteins / immunology
-
Lymphocyte Activation / genetics
-
Lymphocyte Activation / immunology*
-
Male
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Mitogen-Activated Protein Kinase 1 / deficiency*
-
Mitogen-Activated Protein Kinase 1 / genetics*
-
Mitogen-Activated Protein Kinase 1 / physiology
-
Mitogen-Activated Protein Kinase 3 / biosynthesis
-
Mitogen-Activated Protein Kinase 3 / metabolism
-
Molecular Sequence Data
-
Myelin-Oligodendrocyte Glycoprotein
-
Peptide Fragments / administration & dosage
-
Peptide Fragments / immunology
-
T-Lymphocyte Subsets / cytology
-
T-Lymphocyte Subsets / enzymology*
-
T-Lymphocyte Subsets / immunology*
-
Thymus Gland / cytology
-
Thymus Gland / enzymology
-
Thymus Gland / immunology
Substances
-
Glycoproteins
-
Myelin-Oligodendrocyte Glycoprotein
-
Peptide Fragments
-
myelin oligodendrocyte glycoprotein (35-55)
-
Mitogen-Activated Protein Kinase 1
-
Mitogen-Activated Protein Kinase 3