Novel adjuvants for induction of T-cell and antibody responses to encephalitogenic and regulatory determinants in Lewis rats.
Treatment of human autoimmune diseases may be enhanced by using adjuvants that can selectively induce immunoregulatory responses. Two versions of a novel nonionic block copolymer adjuvant suitable for human use, Optivax Oil Formulation (OF) and Optivax Aqueous Formulation (AF), were evaluated for induction of immunity to encephalitogenic and regulatory T-cell receptor (TCR) V-gene determinants. In Lewis rats immunized with myelin basic protein (BP), Optivax OF was more efficient than Optivax AF for inducing delayed type hypersensitivity (DTH), T-cell proliferation, antibodies, and even mild clinical signs of experimental autoimmune encephalomyelitis (EAE). Similarly, Optivax OF was more efficient for inducing inflammatory T-cell and antibody responses to immunoregulatory V beta 8.2 proteins and peptides than Optivax AF, which induced a noninflammatory Th2 response. In general, DTH response to the various immunogens was reflected by increased cellularity and mRNA levels for IFN-gamma in draining lymph nodes, whereas LN cell proliferation without DTH was characterized by increased IL-2 mRNA levels but low or absent IFN-gamma message. These data suggest important differential adjuvant effects of Optivax OF versus Optivax AF on the respective induction of Th1 versus Th2 responses that may be useful in the selective treatment of human immune disorders.
Ariail
K S
KS
Department of Neurology, Oregon Health Sciences University, Portland 97201, USA.
Bebo
B F
BF
Adlard
K
K
Robey
I
I
Burrows
G
G
Newman
M J
MJ
Todd
C W
CW
Vandenbark
A A
AA
Offner
H
H
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D005260:Female; D006967:Hypersensitivity / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology*; D011108:Polymers; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*
D000276:Adjuvants, Immunologic; D001323:Autoantibodies; C113154:CRL 1005; D004676:Myelin Basic Protein; D011108:Polymers