フルイチ　ヨシヒロ   古市　好宏    所属   医学部 医学科（附属足立医療センター）    職種   准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Memory Th1 cells augment tumor-specific CTL following transcutaneous peptide immunization.
掲載誌名	正式名：Cancer research 略　 称：Cancer Res ISSNコード：15387445/00085472
掲載区分	国外
巻・号・頁	68(10),pp.3941-9
著者・共著者	Hosoi Akihiro, Takeda Yayoi, Furuichi Yoshihiro, Kurachi Makoto, Kimura Kiminori, Maekawa Ryuji, Takatsu Kiyoshi, Kakimi Kazuhiro
発行年月	2008/05
概要	Targeting dendritic cells in vivo by transcutaneous peptide immunization (TCI) represents an efficient immunization strategy to induce tumor-specific CTL because it reflects the physiologic conditions occurring during pathogen infection. Here we show that including a Th1 peptide in TCI can activate preexisting memory Th1 (mTh1) responses and thereby enhance the CTL response. For this purpose, peptide-25, a major Th1 epitope of Ag85B from Mycobacterium tuberculosis, was selected. We adoptively transferred peptide-25-specific mTh1 cells and hgp100-specific naive CTL (pmel-1 TCR transgenic) into C57BL/6 mice. Subsequently, mice were transcutaneously immunized with CTL peptide (hgp100) and Th1 peptide (peptide-25). Five days after TCI, the frequency and function of pmel-1 cells was monitored by intracellular IFN-gamma staining, ELISPOT, and in vivo cytotoxicity assays. TCI efficiently expanded hgp100-specific, IFN-gamma-producing, strongly cytotoxic CD8(+) T cells. Concurrent activation of mTh1 cells by peptide-25 induced a 1.5-fold increase in the number of hgp100-specific CTL with enhanced effector functions. Furthermore, TCI elicited not only prophylactic but also therapeutic antitumor responses that were augmented by peptide-25. These results show that TCI facilitates peptide-specific activation of CD4(+) T cells, responsible for the augmenting effect of peptide-25 on the hgp100-specific CTL response. Because a significant proportion of the Japanese population has been vaccinated with Bacillus Calmette-Guerin, they are likely to possess Ag85B- or peptide-25-specific mTh1 cells. Therefore, concomitant activation of Ag85B- or peptide-25-specific mTh1 cells together with tumor-specific CTL by TCI might augment antitumor immune responses in a sizeable fraction of patients.
DOI	10.1158/0008-5472.CAN-08-0032
PMID	18483280