Protection against genital herpes infection in mice immunized under different hormonal conditions correlates with induction of vagina-associated lymphoid tissue.
The present study was undertaken to examine the effect of the hormonal environment on immunization with an attenuated strain of herpes simplex virus type 2 (HSV-2 TK(-)) and subsequent protection against challenge. Ovariectomized mice were administered saline (S; control), estradiol (E(2)), progesterone (P(4)), or a combination of estradiol and progesterone (E+P) and immunized intravaginally (IVAG) with HSV-2 TK(-). Three weeks later, the immunized mice were challenged IVAG with wild-type HSV-2. Mice that were immunized following E treatment were not protected, whereas complete protection against the challenge was seen in mice from the S- and P(4)-treated groups. In the P(4)-treated group, 15% of mice developed chronic pathology following TK(-) immunization. Interestingly, about 40% of the E+P-treated mice were also protected. Upon examination of viral shedding in the vaginal secretions, it was clear that protection against challenge was dependent on the ability of the TK(-) virus to cause productive genital infection under different hormonal conditions. In the protected mice (the S and P groups and part of the E+P group), induced vagina-associated lymphoid tissues composed of CD11c(+) dendritic cells and CD3(+) and CD4(+) T cells were formed transiently in the vaginal lamina propria from day 2 to day 5 postchallenge. These aggregates were absent in the unprotected mice (the E group and part of the E+P group). Significant HSV-2-specific activation of lymphocytes was observed in the local draining lymph nodes of protected mice. This response was absent in the unprotected groups. High titers of gB-specific local immunoglobulin A (IgA) antibodies were present in the vaginal secretions of S- and P(4)-treated immunized mice following HSV-2 challenge. The S-treated group of mice also had high gB-specific IgG titers. These studies show that sex hormones modify the induction of protective immune responses following IVAG immunization.
Gillgrass
Amy E
AE
Department of Pathology, MDCL 4014, McMaster University, 1200 Main St. West, Hamilton, Ontario, Canada.
Tang
Vera A
VA
Towarnicki
Kate M
KM
Rosenthal
Kenneth L
KL
Kaushic
Charu
C
D000818:Animals; D000914:Antibodies, Viral / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D007114:Immunization; D007071:Immunoglobulin A, Secretory / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D008221:Lymphoid Tissue / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D011374:Progesterone / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D014613:Vaccines, Attenuated / Q000494:pharmacology; D014621:Vagina / Q000276:immunology* / Q000473:pathology / Q000821:virology; D014765:Viral Vaccines / Q000494:pharmacology
D000914:Antibodies, Viral; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D011374:Progesterone; D004958:Estradiol