Evidence that NK cells and interferon are required for genetic resistance to lethal infection with ectromelia virus

“…Recovery of resistant mice from a primary ECTV infection depends on the combined actions of mononuclear phagocytes, interferons, and effector functions of natural killer (NK) cells, CD8 ϩ cytotoxic T lymphocyte (CTL), and Ab (5,(15)(16)(17)(18)(19)(20). In addition, we have previously suggested a role for the involvement of type 1 cytokines (21).…”

mentioning

confidence: 99%

Polarized type 1 cytokine response and cell-mediated immunity determine genetic resistance to mousepox

Chaudhri

Panchanathan

Buller

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

168

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“…Various NKG2D ligands have been characterized in mice, including Rae1 and MULT1 [64]. Many different viruses have been shown to induce up-regulation of NKG2D ligands on infected cells in mice and humans [5,[65][66][67]. NKG2DL has also been shown to be relevant in influenza; in-vitro infection of human dendritic cells led to up-regulation of NKG2DL on the infected cells [68].…”

Section: Cd8mentioning

confidence: 99%

“…The resolution of primary viral infections results in accelerated protection against subsequent infection [1][2][3][4][5]. While acute infection has been shown to elicit proliferation of virus-specific CD8 + T cells, this expansion is suggested to be only partly antigen-driven, as limiting dilution analysis has shown only small, variable fractions of T cells to be antigen-specific [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Influenza infection results in local expansion of memory CD8+ T cells with antigen non-specific phenotype and function

Sckisel

Tietze

Zamora

et al. 2013

Clinical and Experimental Immunology

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Summary Primary viral infections induce activation of CD8+ T cells responsible for effective resistance. We sought to characterize the nature of the CD8 + T cell expansion observed after primary viral infection with influenza. Infection of naive mice with different strains of influenza resulted in the rapid expansion of memory CD8 + T cells exhibiting a unique bystander phenotype with significant up-regulation of natural killer group 2D (NKG2D), but not CD25, on the CD44 high CD8+ T cells, suggesting an antigen non-specific phenotype. We further confirmed the non-specificity of this phenotype on ovalbuminspecific (OT-I) CD8 + T cells, which are not specific to influenza. These nonspecific CD8 + T cells also displayed increased lytic capabilities and were observed primarily in the lung. Thus, influenza infection was shown to induce a rapid, antigen non-specific memory T cell expansion which is restricted to the specific site of inflammation. In contrast, CD8 + T cells of a similar phenotype could be observed in other organs following administration of systemic agonistic anti-CD40 and interleukin-2 immunotherapy, demonstrating that bystander expansion in multiple sites is possible depending on whether the nature of activation is either acute or systemic. Finally, intranasal blockade of NKG2D resulted in a significant increase in viral replication early during the course of infection, suggesting that NKG2D is a critical mediator of anti-influenza responses prior to the initiation of adaptive immunity. These results characterize further the local bystander expansion of tissue-resident, memory CD8 + T cells which, due to their early induction, may play an important NKG2D-mediated, antigen non-specific role during the early stages of viral infection.

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“…However, it is known that NK cells are critical for recovery of mice from a primary ECTV infection (5)(6)(7)(8), and recent evidence indicates that memory NK cells can be generated following a primary viral infection and that these cells can respond more rapidly to reinfection with the same pathogen (9)(10)(11). Although it is not entirely correct to categorize NK cells as innate cells, since they exert biological functions that have attributes of both innate and adaptive immunity, for simplicity, we will refer to them as innate cells in this study.…”

mentioning

confidence: 99%

The Orchestrated Functions of Innate Leukocytes and T Cell Subsets Contribute to Humoral Immunity, Virus Control, and Recovery from Secondary Poxvirus Challenge

Tahiliani

Chaudhri

Eldi

et al. 2013

J Virol

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A pivotal role for antigen-specific recall responses to secondary virus infection is well established, but the contribution of innate immune cells to this process is unknown. Recovery of mice from a primary orthopoxvirus (ectromelia virus [ECTV]) infection requires the function of natural killer (NK) cells, granulocytes, plasmacytoid dendritic cells (pDC), T cells, and B cells.However, during a secondary challenge, resolution of infection is thought to be dependent on antibody but not T cell function. We investigated the contribution of NK cells, granulocytes, and pDC to virus control during a secondary virus challenge in mice that had been primed with an avirulent, mutant strain of ECTV. Mice depleted of NK cells, granulocytes, or pDC effectively controlled virus, as did mice depleted of both CD4 and CD8 T cell subsets. However, mice concurrently depleted of all three innate cell subsets had elevated virus load, but this was significantly exacerbated in mice also depleted of CD4 and/or CD8 T cells. Increased viral replication in mice lacking innate cells plus CD4 T cells was associated with a significant reduction in neutralizing antibody. Importantly, in addition to T-dependent neutralizing antibody responses, the function of CD8 T cells was also clearly important for virus control. The data indicate that in the absence of innate cell subsets, a critical role for both CD4 and CD8 T cells becomes apparent and, conversely, in the absence of T cell subsets, innate immune cells help contain infection. S mallpox, caused by variola virus, was considered among the deadliest scourges of humankind. It was eradicated more than 30 years ago through one of the most successful immunization campaigns, which employed a vaccine containing the closely related vaccinia virus (VACV). Although the VACV strain used in the smallpox vaccine is not considered safe by current standards, it was potent in inducing long-lived memory and offered a high degree of protection. Much of our current understanding of protection following vaccination and recall responses to secondary challenge has been inferred from animal studies of closely related poxvirus infections, including mousepox (a disease caused by ectromelia virus [ECTV] in mice), VACV, and monkeypox.We have shown previously that neutralizing antibody, but not the function of CD4 or CD8 T cell subsets, is required to control virus replication during the acute phase of a secondary ECTV challenge (1). In a separate study on monkeypox, depletion of CD4 or CD8 T cells also had no significant effect on virus clearance or on neutralizing antibody production during the acute phase of a secondary challenge in macaques vaccinated with VACV vaccine 6 months previously (2). In both studies, neutralizing antibody produced in the absence of CD4 T cell help (attributed to extrafollicular plasma cells) was sufficient for virus control in immune animals. A number of other studies have found that in vaccinated individuals, humoral immunity to smallpox is stable and lasts longer than memory CD4 and CD8...

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Evidence that NK cells and interferon are required for genetic resistance to lethal infection with ectromelia virus

Cited by 78 publications

References 29 publications

Polarized type 1 cytokine response and cell-mediated immunity determine genetic resistance to mousepox

Polarized type 1 cytokine response and cell-mediated immunity determine genetic resistance to mousepox

Influenza infection results in local expansion of memory CD8+ T cells with antigen non-specific phenotype and function

The Orchestrated Functions of Innate Leukocytes and T Cell Subsets Contribute to Humoral Immunity, Virus Control, and Recovery from Secondary Poxvirus Challenge

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