Proc Natl Acad Sci U S A 2002 Feb
Hurwitz AA, Sullivan TJ, Sobel RA, Allison JP.
Department of Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, NY 13210; Department of Molecular and Cell Biology, Cancer Research Laboratory, and Howard Hughes Medical Institute, University of California, Berkeley, CA 94720; and Department of Pathology, Stanford University School of Medicine and Laboratory Service, Veterans Affairs Medical Center, Palo Alto, CA 94304.
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.