古市　好宏    Department   School of Medicine(Tokyo Women's Medical University Adachi Medical Center), School of Medicine    Position   Associate Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Memory Th1 cells augment tumor-specific CTL following transcutaneous peptide immunization.
Journal	Formal name：Cancer research Abbreviation：Cancer Res ISSN code：15387445/00085472
Domestic / Foregin	Foregin
Volume, Issue, Page	68(10),pp.3941-9
Author and coauthor	Hosoi Akihiro, Takeda Yayoi, Furuichi Yoshihiro, Kurachi Makoto, Kimura Kiminori, Maekawa Ryuji, Takatsu Kiyoshi, Kakimi Kazuhiro
Publication date	2008/05
Summary	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