PMID- 19047439 OWN - NLM STAT- MEDLINE DCOM- 20090210 LR - 20211211 IS - 1540-9538 (Electronic) IS - 0022-1007 (Print) IS - 0022-1007 (Linking) VI - 205 IP - 13 DP - 2008 Dec 22 TI - Dendritic cells and B cells maximize mucosal Th1 memory response to herpes simplex virus. PG - 3041-52 LID - 10.1084/jem.20082039 [doi] AB - Although the importance of cytotoxic T lymphocytes and neutralizing antibodies for antiviral defense is well known, the antiviral mechanism of Th1 remains unclear. We show that Th1 cells mediate noncytolytic antiviral protection independent of direct lysis through local secretion of IFN-gamma after herpes simplex virus (HSV) 2 infection. IFN-gamma acted on stromal cells, but not on hematopoietic cells, to prevent further viral replication and spread throughout the vaginal mucosa. Importantly, unlike other known Th1 defense mechanisms, this effector function did not require recognition of virally infected cells via MHC class II. Instead, recall Th1 response was elicited by MHC class II(+) antigen-presenting cells at the site of infection. Dendritic cells (DCs) were not required and only partially sufficient to induce a recall response from memory Th1 cells. Importantly, DCs and B cells together contributed to restimulating memory CD4 T cells to secrete IFN-gamma. In the absence of both DCs and B cells, immunized mice rapidly succumbed to HSV-2 infection and death. Thus, these results revealed a distinct mechanism by which memory Th1 cells mediate noncytolytic IFN-gamma-dependent antiviral protection after recognition of processed viral antigens by local DCs and B cells. FAU - Iijima, Norifumi AU - Iijima N AD - Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA. FAU - Linehan, Melissa M AU - Linehan MM FAU - Zamora, Melodie AU - Zamora M FAU - Butkus, Debbie AU - Butkus D FAU - Dunn, Robert AU - Dunn R FAU - Kehry, Marilyn R AU - Kehry MR FAU - Laufer, Terri M AU - Laufer TM FAU - Iwasaki, Akiko AU - Iwasaki A LA - eng GR - AI064705/AI/NIAID NIH HHS/United States GR - AI054359/AI/NIAID NIH HHS/United States GR - R01 AI064705/AI/NIAID NIH HHS/United States GR - R01 AI054359/AI/NIAID NIH HHS/United States GR - R01 EB000487/EB/NIBIB NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20081201 PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Antigens, Viral) RN - 0 (Fas Ligand Protein) RN - 0 (Fasl protein, mouse) RN - 0 (fas Receptor) RN - 126465-35-8 (Perforin) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adoptive Transfer MH - Animals MH - Antigens, Viral/immunology MH - B-Lymphocytes/*immunology MH - CD4-Positive T-Lymphocytes/immunology MH - Dendritic Cells/*immunology MH - Fas Ligand Protein/immunology MH - Female MH - Herpesvirus 2, Human/*immunology/physiology MH - Humans MH - Immunologic Memory/*immunology MH - Interferon-gamma/immunology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Mucous Membrane/immunology MH - Perforin/genetics/immunology MH - Th1 Cells/*immunology MH - Vagina/cytology/immunology/virology MH - Virus Replication MH - fas Receptor/immunology PMC - PMC2605233 EDAT- 2008/12/03 09:00 MHDA- 2009/02/12 09:00 PMCR- 2009/06/22 CRDT- 2008/12/03 09:00 PHST- 2008/12/03 09:00 [pubmed] PHST- 2009/02/12 09:00 [medline] PHST- 2008/12/03 09:00 [entrez] PHST- 2009/06/22 00:00 [pmc-release] AID - jem.20082039 [pii] AID - 20082039 [pii] AID - 10.1084/jem.20082039 [doi] PST - ppublish SO - J Exp Med. 2008 Dec 22;205(13):3041-52. doi: 10.1084/jem.20082039. Epub 2008 Dec 1.