Cytotoxic T lymphocyte antigen-4 (CTLA-4) limits the expansion of encephalitogenic T cells in experimental autoimmune encephalomyelitis (EAE)-resistant BALB/c mice.
We and others previously reported that cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates the severity of peptide-induced experimental autoimmune encephalomyelitis (EAE) in mouse strains that are inherently susceptible to the disease. In this report, we show that CTLA-4 engagement also controls disease susceptibility in BALB/c mice, a strain considered to be resistant to EAE induction. Although immunization of BALB/c mice with syngeneic spinal cord homogenate or an I-A(d)-binding myelin peptide antigen failed to result in EAE, immunization with either antigen preparation in conjunction with anti-CTLA-4 resulted in both clinical and histological EAE. CTLA-4 blockade also resulted in a preferential increase in the frequency of antigen-specific T cells secreting IFN-gamma. We conclude that CTLA-4 controls susceptibility in BALB/c mice by limiting the expansion of autoreactive T cells present in the periphery, suggesting a mechanism whereby CTLA-4 contributes to the maintenance of peripheral T cell tolerance to self antigens.
Hurwitz
Arthur A
AA
Department of Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.
Sullivan
Timothy J
TJ
Sobel
Raymond A
RA
Allison
James P
JP
D000069594:Abatacept; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D060908:CTLA-4 Antigen; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D007113:Immunity, Innate / Q000276:immunology; D018796:Immunoconjugates; D007371:Interferon-gamma / Q000378:metabolism; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D018991:Myelin Proteolipid Protein / Q000276:immunology / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D013116:Spinal Cord; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D018991:Myelin Proteolipid Protein; C452640:PLP (40-59) peptide; D010446:Peptide Fragments; D000069594:Abatacept; D007371:Interferon-gamma