Duration of antiviral immunity after smallpox vaccination

Hammarlund, Erika; Lewis, Matthew W.; Hansen, Scott G.; Strelow, Lisa; Nelson, Jay A.; Sexton, Gary; Hanifin, Jon M.; Slifka, Mark K.

doi:10.1038/nm917

Cited by 841 publications

(833 citation statements)

References 42 publications

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“…When the reaction is over, their numbers contract again, first rapidly, then slowly 57, 58, 59. The “half‐life” of blood‐borne antigen‐experienced T cells in the phase of slow contraction shows a tremendous variation, ranging from 8 to 15 years, upon smallpox vaccination of humans60 to less than 40‐60 days, in mice immunized with a peptide of lymphocytic choriomeningitis virus or ovalbumin 59. In mice, the numbers of adoptively transferred and experienced CD4 + and CD8 + T cells decline with half‐lives of 15‐70 days, in the absence of antigen 61, 62.…”

Section: Circulating Memory T Lymphocytesmentioning

confidence: 99%

Immunological memories of the bone marrow

Chang

Tokoyoda

Radbruch

2018

Immunological Reviews

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SummaryMemory for antigens once encountered is a hallmark of the immune system of vertebrates, providing us with an immunity adapted to pathogens of our environment. Despite its fundamental relevance, the cells and genes representing immunological memory are still poorly understood. Here we discuss the concept of a circulating, proliferating, and ubiquitous population of effector lymphocytes vs concepts of resting and dormant populations of dedicated memory lymphocytes, distinct from effector lymphocytes and residing in defined tissues, particularly in barrier tissues and in the bone marrow. The lifestyle of memory plasma cells of the bone marrow may serve as a paradigm, showing that persistence of memory lymphocytes is not defined by intrinsic “half‐lives”, but rather conditional on distinct survival signals provided by dedicated niches. These niches are organized by individual mesenchymal stromal cells. They define the capacity of immunological memory and regulate its homeostasis.

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Section: Circulating Memory T Lymphocytesmentioning

confidence: 99%

Immunological memories of the bone marrow

Chang

Tokoyoda

Radbruch

2018

Immunological Reviews

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“…To measure frequency of MVA-specific T cells, PBMC were stimulated with vaccinia virus (VV, WR strain) (multiplicity of infection=1), anti-CD3 (positive control), or media (negative control) overnight after which Brefeldin A was added for an additional 6 h as described previously (Hammarlund et al 2003). Cells were then harvested and stained with surface antibodies CD4, CD8b, CD28, and CD95 to delineate CM and EM Tcell subsets.…”

Section: Measuring Frequency Of Proliferating T-and B-cell Subsetsmentioning

confidence: 99%

Accelerated immune senescence and reduced response to vaccination in ovariectomized female rhesus macaques

Engelmann

Barron

Urbanski

et al. 2010

AGE

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Aging is associated with a general dysregulation in immune function, commonly referred to as "immune senescence". Several studies have shown that female sex steroids can modulate the immune response. However, the impact of menopauseassociated loss of estrogen and progestins on immune senescence remains poorly understood. To help answer this question, we examined the effect of ovariectomy on T-cell homeostasis and function in adult and aged female rhesus macaques. Our data show that in adult female rhesus macaques, ovariectomy increased the frequency of naïve CD4 T cells. In contrast, ovariectomized (ovx) aged female rhesus macaques had increased frequency of terminally differentiated CD4 effector memory T cells and inflammatory cytokine-secreting memory T cells. Moreover, ovariectomy reduced the immune response (T-cell cytokine and IgG production) following vaccination with modified vaccinia ankara in both adult and aged female rhesus macaques compared to ovary-intact age-matched controls. Interestingly, hormone therapy (estradiol alone or in conjunction with AGE (2011) 33:275-289

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“…Poxvirus-specific Ab titers are stable for the entire human lifespan and T cell immunity is maintained for decades (7,8). Therefore, orthopoxviruses mainly infect unvaccinated individuals.…”

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confidence: 99%

Cowpox Virus Evades CTL Recognition and Inhibits the Intracellular Transport of MHC Class I Molecules

Dasgupta

Hammarlund

Slifka

et al. 2007

The Journal of Immunology

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Orthopoxviruses evade host immune responses by using a number of strategies, including decoy chemokine receptors, regulation of apoptosis, and evasion of complement-mediated lysis. Different from other poxviral subfamilies, however, orthopoxviruses are not known to evade recognition by CTL. In fact, vaccinia virus (VV) is used as a vaccine against smallpox and a vector for eliciting strong T cell responses to foreign Ags. and both human and mouse T cells are readily stimulated by VV-infected APC in vitro. Surprisingly, however, CD8+ T cells of mice infected with cowpox virus (CPV) or VV recognized APC infected with VV but not APC infected with CPV. Likewise, CD8+ T cells from vaccinated human subjects could not be activated by CPV-infected targets and CPV prevented the recognition of VV-infected APC upon coinfection. Because CD8+ T cells recognize viral peptides presented by MHC class I (MHC I), we examined surface expression, total levels, and intracellular maturation of MHC I in CPV- and VV-infected human and mouse cells. Although total levels of MHC I were unchanged, CPV reduced surface levels and inhibited the intracellular transport of MHC I early during infection. CPV did not prevent peptide loading of MHC I but completely inhibited MHC I exit from the endoplasmic reticulum. Because this inhibition was independent of viral replication, we conclude that an early gene product of CPV abrogates MHC I trafficking, thus rendering CPV-infected cells “invisible” to T cells. The absence of this immune evasion mechanism in VV likely limits virulence without compromising immunogenicity.

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Duration of antiviral immunity after smallpox vaccination

Cited by 841 publications

References 42 publications

Immunological memories of the bone marrow

Immunological memories of the bone marrow

Accelerated immune senescence and reduced response to vaccination in ovariectomized female rhesus macaques

Cowpox Virus Evades CTL Recognition and Inhibits the Intracellular Transport of MHC Class I Molecules

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