TY - JOUR
T1 - Dissociating the enhancing and inhibitory effects of pertussis toxin on autoimmune disease
AU - Su, Shao Bo
AU - Silver, Phyllis B.
AU - Wang, Peng
AU - Chan, Chi Chao
AU - Caspi, Rachel R.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - Pertussis toxin (PT) has both enhancing and inhibitory effects on experimental autoimmune disease, depending on its time of administration relative to immunization. The inhibitory effect is due to blocking of G icoupled receptors by the enzymatic A subunit. In this study, we attribute the enhancing effect of PT to the cell-binding B subunit (PT-B). C57BL/6 mice, a strain that requires PT to develop experimental uveitis, were immunized with a retinal Ag and were injected with whole PT, PT-B, or vehicle. Disease and associated immunological responses were evaluated. The results showed that PT-B, determined to be free of biologically significant contamination with whole PT or with endotoxin, was able to mimic all the effects of PT with respect to disease induction, enhancement of delayed-type hypersensitivity, enhancement of lymphocyte proliferation, induction of an innate IL-12 response, and promotion of an adaptive IFN-γ response to the uveitogenic Ag. Our results suggest that PT-B is largely responsible for the disease-enhancing properties of PT.
AB - Pertussis toxin (PT) has both enhancing and inhibitory effects on experimental autoimmune disease, depending on its time of administration relative to immunization. The inhibitory effect is due to blocking of G icoupled receptors by the enzymatic A subunit. In this study, we attribute the enhancing effect of PT to the cell-binding B subunit (PT-B). C57BL/6 mice, a strain that requires PT to develop experimental uveitis, were immunized with a retinal Ag and were injected with whole PT, PT-B, or vehicle. Disease and associated immunological responses were evaluated. The results showed that PT-B, determined to be free of biologically significant contamination with whole PT or with endotoxin, was able to mimic all the effects of PT with respect to disease induction, enhancement of delayed-type hypersensitivity, enhancement of lymphocyte proliferation, induction of an innate IL-12 response, and promotion of an adaptive IFN-γ response to the uveitogenic Ag. Our results suggest that PT-B is largely responsible for the disease-enhancing properties of PT.
UR - http://www.scopus.com/inward/record.url?scp=0042430414&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.171.5.2314
DO - 10.4049/jimmunol.171.5.2314
M3 - Article
C2 - 12928376
AN - SCOPUS:0042430414
SN - 0022-1767
VL - 171
SP - 2314
EP - 2319
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -