CD4+ T helper cell response is required for memory in CD8+ T lymphocytes induced by a poly(I:C)-adjuvanted MHC I-restricted peptide epitope.
It was known that double-stranded RNA (dsRNA) has vaccine adjuvant activity by acting through the dsRNA/toll-like receptor (TLR)3 signaling. More recently, it was reported that immunization of mice with a poly(I:C)-adjuvanted major histocompatibility (MHC) class I-restricted peptide epitope derived from a tumor-specific antigen protein induced strong tumor-killing CD8 CTL responses. However, it remains unclear whether the poly(I:C) can help an MHC class I-restricted peptide epitope to induce a strong and functional memory CD8 CTL response in the absence of a T helper (TH) response. By using in vivo CTL and direct tumor challenging assays, we demonstrated that, although poly(I:C) as a vaccine adjuvant significantly enhanced the immune responses induced by an MHC I-restricted peptide epitope, MHC class II-restricted TH cell responses were still required to generate memory CTL responses. The MHC class II-restricted TH epitopes can be cognate, noncognate, or even from the necrotic bodies of un-related tumor cells. Thus, future efforts of using synthetic dsRNA as an adjuvant to induce specific and long-lasting memory CTL immune responses should include the provision of an appropriate TH cell response.
Qiu
Fu
F
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA.
Cui
Zhengrong
Z
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D000939:Epitopes / Q000276:immunology / Q000494:pharmacology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000494:pharmacology; D007156:Immunologic Memory; D051379:Mice; D010455:Peptides / Q000276:immunology / Q000494:pharmacology; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000276:immunology / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D012330:RNA, Double-Stranded; D011070:Poly I-C