IL-12-Dependent enhancement of CTL response to weak class I-restricted peptide immunogens requires coimmunization with T helper cell immunogens.
The effect of in vivo administration of rmIL-12 on the CTL response to immunization with a weakly immunogenic class I-restricted peptide emulsified in incomplete Freund's adjuvant was investigated. In the absence of IL-12, peptide-specific CTL responses were significantly greater following coimmunization with class I-restricted peptide and T helper cell antigens than following immunization with the class I-restricted peptide alone. IL-12-dependent enhancement of the CTL response to peptide immunization was demonstrated in the presence of, but not in the absence of, coimmunization with T helper cell antigen. These findings indicate that IL-12 enhancement of the CTL response to weak class I-restricted immunogens is T helper cell dependent. Treatment with rmIL-12 also enhanced the CTL response to immunization with cDNA encoding both CTL and T helper cell epitopes. These findings are relevant to the design of vaccines containing tumor-associated class I-restricted peptides currently being tested as an immunotherapy for cancer patients.
Swiniarski
H
H
Genetics Institute, One Burtt Road, Andover, Massachusetts 01810, USA.
Wolf
S F
SF
Sturmhoefel
K
K
Peterson
R L
RL
Dorner
A J
AJ
O'Toole
M
M
D000818:Animals; D000941:Antigens / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000502:physiology; D005260:Female; D005620:Freund's Adjuvant; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007114:Immunization; D018664:Interleukin-12 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D011506:Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000941:Antigens; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D011506:Proteins; D018664:Interleukin-12; D005620:Freund's Adjuvant