Antibodies and CD8+ T Cells Are Complementary and Essential for Natural Resistance to a Highly Lethal Cytopathic Virus

Fang, Min; Sigal, Luis J.

doi:10.4049/jimmunol.175.10.6829

Cited by 114 publications

(150 citation statements)

References 53 publications

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“…Resistant strains such as C57BL/6 (B6) do not show any symptoms of mousepox due to the strong innate and T cell responses during early infection and the Ab response at the later stages (31)(32)(33)(34). In this report we show that CD28 KO mice (in a B6-resistant background) are sensitive to mousepox.…”

Section: Direct Cd28 Costimulation Is Required For Cd8mentioning

confidence: 58%

“…ϩ T cells readily kill infected targets in vitro (33). Thus, although a direct demonstration that all GzB ϩ CD8 ϩ cells are virus specific is not possible in this context, the cytotoxicity assays strongly suggest that they are virus specific and not the result of bystander activation.…”

Section: Cd8mentioning

confidence: 98%

“…The production of ECTV and VACV stocks and the determination of titers in stocks and organs were done as described previously (33,36). All mice were bred at the Fox Chase Cancer Center Laboratory Animal Facility in specific pathogen free rooms or purchased from Jackson Laboratories.…”

Section: Viruses Mice and Infectionsmentioning

confidence: 99%

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Direct CD28 Costimulation Is Required for CD8+ T Cell-Mediated Resistance to an Acute Viral Disease in a Natural Host

Fang

Sigal

2006

The Journal of Immunology

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Previous studies have suggested that, differing from model Ags, viruses that replicate extensively in the host still induce normal CD8+ T cell responses in the absence of CD28 costimulation. Because these studies were performed with viruses that do not normally cause acute disease, an important remaining question is whether CD28 costimulation is required for CD8+ T cell-mediated resistance to widely replicating but pathogenic viruses. To address this question, we studied the role of CD28 costimulation in CD8+ T cell-mediated resistance to mousepox, a disease of the mouse caused by the natural mouse pathogen, the ectromelia virus (ECTV). C57BL/6 (B6) mice are naturally resistant to mousepox, partly due to a fast and strong CD8+ T cell response. We found that B6 mice deficient in CD28 (CD28 knockout (KO)) are highly susceptible to lethal mousepox during the early stages of ECTV infection but can be protected by immunization with the antigenically related vaccinia virus (VACV) or by adoptive transfer of CD28 KO anti-VACV memory CD8+ cells. Of interest, a thorough comparison of the CD8+ T cell responses to ECTV and VACV suggests that the main reason for the susceptibility of CD28 KO mice to mousepox is a reduced response at the early stages of infection. Thus, while in the absence of CD28 costimulation the end point strength of the T cell responses to nonpathogenic viruses may appear normal, CD28 costimulation increases the speed of the T cell response and is essential for resistance to a life-threatening acute viral disease.

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Section: Direct Cd28 Costimulation Is Required For Cd8mentioning

confidence: 58%

Section: Cd8mentioning

confidence: 98%

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Direct CD28 Costimulation Is Required for CD8+ T Cell-Mediated Resistance to an Acute Viral Disease in a Natural Host

Fang

Sigal

2006

The Journal of Immunology

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“…The Ab response to poxviruses is almost completely Th dependent (12,47,60). Therefore, depleting CD4 ϩ T cells also eliminates Ab responses (12,47,60). To address the contributions of enhanced nAb and CD8 ϩ T cell responses during infection with vv-VCPko, we depleted mice of CD8 ϩ and CD4 ϩ T cells individually or together and examined lesion sizes (Fig.…”

Section: Cd8 ؉ T Cells and Cd4 ؉ T Cells Contribute To Attenuation Ofmentioning

confidence: 99%

The Vaccinia Virus Complement Control Protein Modulates Adaptive Immune Responses during Infection

Girgis

DeHaven

Xiao

et al. 2011

J Virol

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“…[3][4][5][6][7][8][9] More recently, along with others, we defined some parameters critical for recovery from a secondary ECTV infection. [10][11][12][13] It has become apparent that antibody (Ab) has a critical role in recovery from secondary ECTV infection whereas the role of CD8 T cells has become questionable.…”

mentioning

confidence: 99%

Antiviral protection following immunization correlates with humoral but not cell‐mediated immunity

2010

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Smallpox was a deadly disease when it was rife yet despite its eradication more than 30 years ago, the possibility of accidental or intentional release has driven research in search of better definitions of correlates of protective immunity. Mousepox, a disease caused by ectromelia virus (ECTV), is arguably one of the best surrogate small animal models for smallpox. Correlates of protection in mousepox are well defined during primary infection, whereas those in a secondary infection, which have definite relevance to vaccination strategies, are less well understood. We previously established that neutralizing antibody (Ab), which is generated far more rapidly during a secondary infection compared with a primary infection, has a key role during a secondary virus challenge. In this study, we show that the route of immunization or the use of homologous or heterologous virus vaccines for immunization does not influence the ability of mice to control high-dose virulent ECTV challenge or to mount a substantial secondary neutralizing Ab response. In contrast, the recall cytotoxic T lymphocyte (CTL) responses generated under these regimes of immunization were varied and did not correlate with virus control. Furthermore, unlike the recall Ab response that was generated rapidly, the kinetics of the secondary antiviral CTL response was no different to a primary infection and peaked only at day 8 post-challenge. This finding further underscores the importance of Ab in conferring protection during secondary poxvirus infection. This information could potentially prove useful in the design of safer and more efficacious vaccines against poxviruses or other diseases using poxvirus vectors. Keywords: antibody; cytotoxic T lympohocyte; memory; poxvirus infection protective immunity; vaccination Smallpox was an ancient scourge, causing mortality rates as high as 30-40% in the past. 1 Fortunately, this deadly disease was eradicated through the highly successful smallpox eradication campaign involving vaccination. 1 Fears of an intentional or accidental release of variola virus, the causative agent of smallpox, have sparked interest in understanding the correlates of protection in smallpox. Very little is known regarding protective immunity to smallpox as the currently available tools of molecular biology, immunology and virology were not available at the time the disease was rife. Furthermore, the fact that the currently licensed vaccine for smallpox has unacceptable rates of adverse effects emphasizes not only the need to understand immunity to smallpox but also to develop effective and safer vaccination strategies. 2 In the absence of clinical cases of smallpox, surrogate animal models such as variola virus and monkeypox virus (MPXV) infection in macaques and vaccinia (VACV) and ectromelia virus (ECTV) infection in mice have been used to infer requirements for recovery and protection from smallpox. Both ECTV and variola virus are highly virulent, cause disease with high mortality rates in their respective natural hosts and share ma...

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Antibodies and CD8+ T Cells Are Complementary and Essential for Natural Resistance to a Highly Lethal Cytopathic Virus

Cited by 114 publications

References 53 publications

Direct CD28 Costimulation Is Required for CD8+ T Cell-Mediated Resistance to an Acute Viral Disease in a Natural Host

Direct CD28 Costimulation Is Required for CD8+ T Cell-Mediated Resistance to an Acute Viral Disease in a Natural Host

The Vaccinia Virus Complement Control Protein Modulates Adaptive Immune Responses during Infection

Antiviral protection following immunization correlates with humoral but not cell‐mediated immunity

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