The Journal of Experimental Medicine
Janeway's Immunobiology 7th Edition
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Published online 13 January 2003 doi:10.1084/jem.20021109
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© Rockefeller University Press, 0022-1007/2003/1/153 $5.00
The Journal of Experimental Medicine, Volume 197, Number 2, 153-162

Vaginal Submucosal Dendritic Cells, but Not Langerhans Cells, Induce Protective Th1 Responses to Herpes Simplex Virus-2

Xinyan Zhao1, Eszter Deak1, Kelly Soderberg1, Melissa Linehan1, David Spezzano2, Jia Zhu2, David M. Knipe2 and Akiko Iwasaki1

1 Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520
2 Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115

Address correspondence to Akiko Iwasaki, Dept. of Epidemiology and Public Health, 60 College St., LEPH 716, New Haven, CT 06520. Phone: 203-785-2919; Fax: 203-785-7552; E-mail: akiko.iwasaki{at}yale.edu

Herpes simplex virus (HSV) type 2 infection occurs primarily at the genital mucosal surfaces and is a leading cause of ulcerative lesions. Despite the availability of animal models for HSV-2 infection, little is known regarding the mechanism of immune induction within the vaginal mucosa. Here, we examined the cell types responsible for the initiation of protective Th1 immunity to HSV-2. Intravaginal inoculation of HSV-2 led to a rapid recruitment of submucosal dendritic cells (DCs) to the infected epithelium. Subsequently, CD11c+ DCs harboring viral peptides in the context of MHC class II molecules emerged in the draining lymph nodes and were found to be responsible for the stimulation of IFN{gamma} secretion from HSV-specific CD4+ T cells. Other antigen-presenting cells including B cells and macrophages did not present viral peptides to T cells in the draining lymph nodes. Next, we assessed the relative contribution to immune generation by the Langerhans cells in the vaginal epithelium, the submucosal CD11b+ DCs, and the CD8{alpha}+ lymph node DCs. Analysis of these DC populations from the draining lymph nodes revealed that only the CD11b+ submucosal DCs, but not Langerhans cell–derived or CD8{alpha}+ DCs, presented viral antigens to CD4+ T cells and induced IFN{gamma} secretion. These results demonstrate a previously unanticipated role for submucosal DCs in the generation of protective Th1 immune responses to HSV-2 in the vaginal mucosa, and suggest their importance in immunity to other sexually transmitted diseases.

Key Words: genital mucosa • cytokines • lymph node • epithelium • sexually transmitted disease


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