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Augmented induction of CD8 + cytotoxic T‐cell response and antitumour resistance by T helper type 1‐inducing peptide

2005; Wiley; Volume: 117; Issue: 1 Linguagem: Inglês

10.1111/j.1365-2567.2005.02262.x

1365-2567

Takeshi Kikuchi, Shuichiro Uehara, Haruyuki Ariga, Takeshi Tokunaga, Ai Kariyone, Toshiki Tamura, Kiyoshi Takatsu,

T-cell and B-cell Immunology

Summary The effector CD8 + T cells recognize major histocompatibility complex (MHC) class I binding altered self‐peptides expressed in tumour cells. Although the requirement for CD4 + T helper type 1 (Th1) cells in regulating CD8 + T cells has been documented, their target epitopes and functional impact in antitumour responses remain unclear. We examined whether a potent immunogenic peptide of Mycobacterium tuberculosis eliciting Th1 immunity contributes to the generation of CD8 + T cells and to protective antitumour immune responses to unrelated tumour‐specific antigens. Peptide‐25, a major Th epitope of Ag85B from M. tuberculosis preferentially induced CD4 + Th1 cells in C57BL/6 mice and had an augmenting effect on Th1 generation for coimmunized unrelated antigenic peptides. Coimmunization of mice with Peptide‐25 and ovalbumin (OVA) or Peptide‐25 and B16 melanoma peptide [tyrosinase‐related protein‐2 (TRP‐2)] for MHC class I led to a profound increase in CD8 + T cells specific for OVA and TRP‐2 peptides, respectively. This heightened response depended on Peptide‐25‐specific CD4 + T cells and interferon‐γ‐producing T cells. In tumour protection assays, immunization with Peptide‐25 and OVA resulted in the enhancement of CD8 + cytotoxic cell generation specific for OVA and the growth inhibition of EL‐4 thymoma expressing OVA peptide leading to the tumour rejection. These phenomena were not achieved by immunization with OVA alone. Peptide‐25‐reactive Th1 cells counteractivated dendritic cells in the presence of Peptide‐25 leading them to activate and present OVA peptide to CD8 + cytotoxic T cells.