ABSTRACT
Dendritic cells (DCs) have been demonstrated to be an important if not essential inducer of cellular immune responses. The ability to grow these cells in vitro may open up new avenues for protective immunizations. In this study we have analyzed the virus-specific memory response generated following immunization with ex vivo-infected bone marrow-derived dendritic cells. We demonstrate that mouse DCs are efficiently infected with influenza virus but do not release infectious progeny virus. Ex vivo-infected DCs secrete interleukin-12 (IL-12) and induce a potent T helper (Th)1-like immune response when injected into mice. This was demonstrated by the generation of cytotoxic T lymphocytes, the production of high levels of gamma-interferon, and undetectable levels of IL-4 upon in vitro restimulation of splenocytes from immunized animals. In addition, the virus-specific antibody response is primarily of the IgG2a isotype, consistent with the expansion of Th1 cells. Animals immunized with DCs infected with X-31 influenza virus and challenged with PR8 influenza virus cleared the infection faster than animals not vaccinated. Thus, infected DCs efficiently activate the cellular immune response and induce heterosubtypic immunity in mice.
Subject(s)
Adoptive Transfer/methods , Dendritic Cells/immunology , Dendritic Cells/virology , Influenza A virus/immunology , Animals , Antigens, Viral/immunology , Bone Marrow Cells/immunology , Bone Marrow Cells/pathology , Bone Marrow Cells/virology , Cell Differentiation/immunology , Cell Line , Cells, Cultured , Dendritic Cells/pathology , Dendritic Cells/transplantation , Disease Models, Animal , Dogs , Female , Immunologic Memory , Influenza A virus/classification , Influenza A virus/pathogenicity , Injections, Intraperitoneal , Lymphocyte Activation , Mice , Mice, Inbred BALB C , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/pathology , Orthomyxoviridae Infections/virology , Recurrence , Species Specificity , Stem Cells/immunology , Stem Cells/virology , T-Lymphocytes, Cytotoxic/immunology , T-Lymphocytes, Cytotoxic/virology , Th1 Cells/immunology , Th1 Cells/metabolism , Th1 Cells/virology , Virion/growth & development , Virion/pathogenicityABSTRACT
Thymidine kinase (TK) inhibitors can block the activity of TK-dependent antiviral drugs in vitro. We have examined the ability of the TK inhibitor (+/-)-9-([(Z)-2-(hydroxymethyl)cyclohexyl] methyl)guanine (L-653,180) to prevent the therapeutic effect of acyclovir (ACV) in experimental herpes simplex virus type 1 (HSV) skin infections of mice. The results showed that ACV given in the drinking water prevents, in a dose-dependent way, the evolution of the viral infection, and that L-653,180 can reverse some of the therapeutic effects of the antiviral drug. Among the parameters used to evaluate the effect of the TK inhibitor mortality was increased compared to ACV treatment alone, only in the presence of low doses of ACV, whereas the establishment of latent infections in sensory ganglia was significantly increased compared to ACV treatment alone, even when high doses of ACV were administered together with L-653,180.
Subject(s)
Acyclovir/antagonists & inhibitors , Guanine/analogs & derivatives , Herpes Simplex/drug therapy , Thymidine Kinase/antagonists & inhibitors , Acyclovir/administration & dosage , Acyclovir/therapeutic use , Animals , Dose-Response Relationship, Drug , Female , Ganglia/drug effects , Ganglia/microbiology , Guanine/administration & dosage , Guanine/pharmacology , Guanine/therapeutic use , Herpes Simplex/complications , Mice , Mice, HairlessABSTRACT
Herpes simplex virus was frequently isolated from ipsilateral popliteal lymph nodes after percutaneous inoculation of the dorsal face of the footpad, and from ipsi- and contralateral submandibular lymph nodes after percutaneous inoculation of the cheek or the orofacial area of mice. Virus was detected only on very rare occasion in nondraining lymph nodes (inguinal or axillary) or in contralateral popliteal lymph nodes, but was frequently isolated in contralateral lumbar lymph nodes after footpad inoculation. The presence of virus in lymph nodes paralleled or followed the invasion of ipsilateral sensory ganglia and was associated with dissemination of virus in contralateral sensory ganglia after unilateral inoculation. In older mice virus was detected only occasionally in lymph nodes and dissemination of virus in contralateral sensory ganglia was generally not observed. The results suggest that lymphatic spread may contribute to dissemination of virus in contralateral sensory ganglia after unilateral inoculation of mice.
Subject(s)
Herpes Simplex/microbiology , Lymph Nodes/microbiology , Simplexvirus/growth & development , Age Factors , Animals , Ganglia, Spinal/microbiology , Mice , Time Factors , Trigeminal Ganglion/microbiologyABSTRACT
A double-blind, placebo-controlled study was done to evaluate the efficacy of an alpha interferon preparation in 128 patients with recurrent genital herpes. The preparation containing 10(5) or 10(7) U alpha interferon with nonoxynol 9 in a cream base (Exovir-HZ) was applied three times daily for 5 days. The treatment did not cause any adverse reactions. Patients treated with either interferon concentration became negative for viral culture at a faster rate than placebo recipients. The end of new lesion formation, scabbing, and the healing of lesions were all superior in patients treated with 10(5) U to those treated with 10(7) U interferon. End of new lesion formation and scabbing were also statistically different in patients treated with 10(7) U from those patients treated with placebo. Results suggest that topical interferon might be useful in relieving symptoms of severe cases of genital herpes.
