Genetic background determines the requirement for B7 costimulation in induction of autoimmunity
Copyright policy )Genetic background determines the requirement for B7 costimulation in induction of autoimmunity
B7 costimulatory molecules play an important role in inducing autoimmunity, tumor immunity, and transplant rejection, and therapeutic manipulation of B7 is being investigated in human diseases. To determine whether B7 costimulation is essential for inducing autoimmunity on different genetic backgrounds, we backcrossed B7.1/B7.2 deficient ((-/-)) mice on to the C57BL/6 (B6) and SJL backgrounds and induced experimental autoimmune encephalomyelitis (EAE) in these mice. B7.1/B7.2(-/-) mice on the B6 background were resistant to EAE induced with MOG 35-55, whereas the SJL B7.1/B7.2(-/-) mice were susceptible to PLP 139-151 or PLP 178-191-induced EAE. The SJL B7.1/B7.2(-/-) mice had a qualitatively different lesion pattern in that they showed increased white matter vacuolation compared to wild-type SJL mice when immunized with either PLP 139-151 or PLP 178-191. (B6xSJL)F1 B7.1/B7.2(+/+) mice were susceptible to EAE whereas (B6xSJL)F1 B7.1/B7.2(-/-) mice were resistant to EAE induced with either encephalitogenic peptide. Thus, genetic background determines the B7 requirement for inducing autoimmunity. These data have important implications for developing B7-based immunotherapies for human diseases.
- Brigham and Women's Faulkner Hospital United States
- Veterans Health Administration United States
- University of California, San Francisco United States
- Harvard University United States
- Stanford University United States
Male, Multiple Sclerosis, Encephalomyelitis, Autoimmune, Experimental, Immunoconjugates, Immunology, Molecular Sequence Data, Autoimmunity, Neurodegenerative, Crosses, Inbred C57BL, Lymphocyte Activation, Autoimmune Disease, Abatacept, Experimental, Mice, Genetic, Antigens, CD, 2.1 Biological and endogenous factors, Animals, CTLA-4 Antigen, Genetic Predisposition to Disease, Amino Acid Sequence, Aetiology, Antigens, Encephalomyelitis, Myelin Proteolipid Protein, Crosses, Genetic, Glycoproteins, Membrane Glycoproteins, Biomedical and Clinical Sciences, Neurosciences, Antigens, Differentiation, Peptide Fragments, Brain Disorders, CD, Differentiation, B7-1 Antigen, Myelin-Oligodendrocyte Glycoprotein, Female, Immunization, B7-2 Antigen, Lymph Nodes, Autoimmune
Male, Multiple Sclerosis, Encephalomyelitis, Autoimmune, Experimental, Immunoconjugates, Immunology, Molecular Sequence Data, Autoimmunity, Neurodegenerative, Crosses, Inbred C57BL, Lymphocyte Activation, Autoimmune Disease, Abatacept, Experimental, Mice, Genetic, Antigens, CD, 2.1 Biological and endogenous factors, Animals, CTLA-4 Antigen, Genetic Predisposition to Disease, Amino Acid Sequence, Aetiology, Antigens, Encephalomyelitis, Myelin Proteolipid Protein, Crosses, Genetic, Glycoproteins, Membrane Glycoproteins, Biomedical and Clinical Sciences, Neurosciences, Antigens, Differentiation, Peptide Fragments, Brain Disorders, CD, Differentiation, B7-1 Antigen, Myelin-Oligodendrocyte Glycoprotein, Female, Immunization, B7-2 Antigen, Lymph Nodes, Autoimmune
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