Dendritic cells and B cells maximize mucosal Th1 memory response to herpes simplex virus.
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.
Iijima
Norifumi
N
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Linehan
Melissa M
MM
Zamora
Melodie
M
Butkus
Debbie
D
Dunn
Robert
R
Kehry
Marilyn R
MR
Laufer
Terri M
TM
Iwasaki
Akiko
A
D019264:Adoptive Transfer; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D053222:Fas Ligand Protein / Q000276:immunology; D005260:Female; D018258:Herpesvirus 2, Human / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000276:immunology; D054353:Perforin / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D014621:Vagina / Q000166:cytology / Q000276:immunology / Q000821:virology; D014779:Virus Replication; D019014:fas Receptor / Q000276:immunology
D000956:Antigens, Viral; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D019014:fas Receptor; D054353:Perforin; D007371:Interferon-gamma