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.
Subject(s)
Lymphocyte Activation/immunology , Mitogen-Activated Protein Kinase 1/deficiency , Mitogen-Activated Protein Kinase 1/genetics , T-Lymphocyte Subsets/enzymology , T-Lymphocyte Subsets/immunology , 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 , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , 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 , Thymus Gland/cytology , Thymus Gland/enzymology , Thymus Gland/immunologyABSTRACT
The morbidity and mortality of infectious diseases are significantly increased in aged humans. Hence, vaccination has been suggested as a means to reduce or prevent the impact of infections on old individuals. However, it has remained unresolved whether or not standard vaccine adjuvants such as aluminum hydroxide (Alum) are similarly efficacious in old individuals, as compared to young adults. Here, we have investigated the effects of prototypic immunological adjuvants, complete Freund's adjuvant (CFA), incomplete Freund's adjuvant (IFA), or Alum on HEL-specific T cell responses in young adult and old mice. We report that independent of the adjuvant used, the induced T cell responses to the prototypic protein antigen hen eggwhite lysozyme (HEL) were similar in young adult and old mice in terms of cytokine production, T cell frequencies, determinant specificity, and T cell repertoire. The results suggest that vaccine adjuvants developed in young adults should be equally effective in inducing T cell immunity in old individuals.