Intraepithelial γδ T Cells May Bridge a Gap between Innate Immunity and Acquired Immunity to Herpes Simplex Virus Type 2 (original) (raw)
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Journal of General Virology, 2001
The role of B, CD4+ T and CD8+ T cells in both primary genital infection with attenuated herpes simplex virus type 2 (HSV-2) and development of protective immunity to a later challenge with virulent HSV-2 using lymphocyte-deficient mice has been elucidated. Following primary inoculation with attenuated thymidine kinase-deficient (TK−) HSV-2, B cell-deficient (μMT) mice developed a local viraemia and transient genital inflammation, suggesting a role for B cells in the innate control of local infection and inflammation. Natural antibodies are implicated in this process, as passive transfer of normal serum into μMT mice significantly reduced HSV-2 TK− shedding in the vaginal lumen, although it did not affect subsequent inflammation. Protection against lethal HSV-2 challenge was noted in HSV-2-vaccinated wild-type, CD8+ T cell-deficient and μMT mice and was characterized by strong virus-specific IFN-γ responses in vitro and delayed type hypersensitivity (DTH) responses in vivo. In contr...
The Journal of Infectious Diseases, 2004
Herpes simplex virus (HSV)-specific T cells are essential to control and resolve genital herpes (GH). To investigate the potential involvement of gd T cells in GH, T cells were recovered and expanded, by mitogenic stimulation, to T cell lines from the genital lesions of 17 patients with GH and 5 control subjects who had other diseases. Relatively high numbers of gd T cells-predominantly, Vg9Vd2 T cells-were detected only in the T cell lines of the patients with GH. Intralesional Vg9Vd2 T cell clones did not recognize HSV-infected cells, but they showed reactivity to isopentenyl pyrophosphate and Daudi cells. The T cell clones secreted interferon-g, tumor necrosis factor-a, interleukin (IL)-8, macrophage inflammatory protein-1a, and RANTES (regulated on activation, normally T cell expressed or secreted), but they secreted no or limited IL-4. The results of the present study suggest the infiltration and putative involvement of isopentenyl pyrophosphate-reactive Vg9Vd2 T helper 1-like cells in individuals with GH. Genital herpes (GH), which affects the genital tract and is predominantly caused by herpes simplex virus (HSV) type 2 (HSV-2), is one of the most prevalent sexually transmitted diseases worldwide. The local HSV-specific adaptive immune response is considered to play a pivotal role in controlling the infection [1]. As for other viral infections, innate immune cells, such as macrophages, NK cells, and gd T cells, have been suggested to play a protective role in HSV infections [2].
Archives of Virology, 1987
Herpes simplex virus type 2 is a human venereal pathogen which causes lethal neurological illness after intravaginal inoculation into B A L B / e J mice. In the present studies, we demonstrate that intravaginM vaccination with an attenuated strain of this virus, which possesses a partial deletion of the thymidine kinase gene, rapidly induced durable immunity to lethal intravaginal ehMlenge with wild-type virus. Such immunity was characterized by a dramatic hyperplasia of genital lymph nodes and a significant reduction in wild-type virus replication and spread :from the genital tract following lethal challenge. Of g r e a~r importance, immunity to lethal wild-type virus ehMlenge in the genital tract was transferrable to non-immune mice with genital lymph node cells prepared 1 week after intravaginal vaccination but was not transferrable with serum or cells from other lymphoid organs tested at this time. The adoptive transfer of anti-viral immunity to wild-type challenge was also characterized by a diminution in wild-type virus replication and spread from the genital tract. These results suggest that an important component of cellular immunity to genital pathogens may be antigenic stimulation of genital lymph nodes. 3 Corresponding author; telephone (416) 525-9140, ext. 2473. 52 M.R. McDERMOTT et al.:
Innate and adaptive immunity against herpes simplex virus type 2 in the genital mucosa
Journal of Reproductive Immunology, 2011
Herpes simplex virus type 2 (HSV-2) is becoming increasingly prevalent worldwide, despite the widespread use of antiviral drugs. Its ability to evade the immune system and establish a latent infection has made it difficult to develop an effective vaccine. Our understanding of the immune response against HSV-2 remains complex and involves a balance between innate signaling pathways and the adaptive immune response. Primary infection with HSV-2 induces toll-like receptor (TLR)-mediated Type I interferon (IFN) production, which establishes an antiviral state and activates multiple cell types, including natural killer cells and plasmacytoid dendritic cells. This innate response is not only crucial for controlling initial infection, but also for priming adaptive immune responses as well. Both humoral and cellular responses encompass adaptive immunity, although the former has been shown to be dispensable in response to HSV-2. Recently, numerous studies have attributed IFNγ producing CD4+ T cells to be the key effector molecule responsible for clearing infection. It remains unclear whether regulatory T (Treg) cells are a source of aid or hindrance in the clearance of disease. Collectively, this review highlights the balance between innate and adaptive effector responses that contribute to the control and clearance of HSV-2 infection.
Journal of Experimental Medicine, 2003
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 IFNγ 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, ...
Journal of virology, 1984
Herpes simplex virus type 2 is a common human venereal pathogen which causes lethal neurological illness after intravaginal inoculation into BALB/cJ mice. To investigate whether an attenuated, nonlethal strain of this virus would confer immunity after inoculation of mice, we constructed a strain containing a partial deletion of the thymidine kinase gene, which is necessary for viral replication and spread in sensory ganglia. Unlike its wild-type counterpart, this deletion-containing strain of herpes simplex virus type 2 caused mild clinical disease and was not lethal when studied in an age-dependent murine model of intravaginal infection. Furthermore, after intravaginal infection, the deletion-containing strain could not be isolated from sensory ganglia at a time when wild-type virus was abundant. Of greater significance, intravaginal inoculation with the deletion-containing strain rendered mice completely resistant to rechallenge with a 10-fold 50% lethal dose of wild-type virus. T...
International Immunology, 1997
V γ 4/V δ 1 TCR, their exclusive use of γ chain homodimers in their TCR, and the absence of CD2 and CD28 co-stimulatory molecules are a novel combination of properties that suggests specialized functional properties. Although vaginal γδ T cells share some features in common with γδ T cells that reside in other epithelial tissues, such as skin and intestine, the present studies provide additional evidence that vaginal γδ T cells are a highly specialized and distinct T cell population.