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

Abstract

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.