Elevated Frequency of Gamma Interferon-Producing NK Cells in Healthy Adults Vaccinated against Influenza Virus

Long, Brian; Michaëlsson, Jakob; Loo, Christopher; Ballan, Wassim; Vu, Bien-Aimee N.; Hecht, Frederick M.; Lanier, Lewis L.; Chapman, J.N.; Nixon, Douglas F.

doi:10.1128/cvi.00357-07

Cited by 63 publications

(57 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fifth, the phenotypes of cells responding in ELISpot assays are unknown. It can be speculated that NK cells are among the cells that have responded in our ELISpot assay (15).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Studies of cell‐mediated immune responses to influenza vaccination in systemic lupus erythematosus

Holvast¹,

Assen²,

Haan³

et al. 2009

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. Both antibody and cell-mediated responses are involved in the defense against influenza. In patients with systemic lupus erythematosus (SLE), a decreased antibody response to subunit influenza vaccine has been demonstrated, but cell-mediated responses have not yet been assessed. This study was therefore undertaken to assess cell-mediated responses to influenza vaccination in patients with SLE.Methods. Fifty-four patients with SLE and 54 healthy control subjects received subunit influenza vaccine. Peripheral blood mononuclear cells and sera were obtained before and 1 month after vaccination. Cellmediated responses to A/H1N1 and A/H3N2 vaccines were evaluated using an interferon-␥ (IFN␥) enzymelinked immunospot assay and flow cytometry. Antibody responses were measured using a hemagglutination inhibition test.Results. Prior to vaccination, patients with SLE had fewer IFN␥ spot-forming cells against A/H1N1 compared with control subjects and a lower frequency of IFN␥-positive CD8؉ T cells. After vaccination, the number of IFN␥ spot-forming cells increased in both patients and control subjects, although the number remained lower in patients. In addition, the frequencies of CD4؉ T cells producing tumor necrosis factor and interleukin-2 were lower in patients after vaccination compared with healthy control subjects. As expected for a subunit vaccine, vaccination did not induce a CD8؉ T cell response. For A/H3N2-specific responses, results were comparable. Diminished cell-mediated responses to influenza vaccination were associated with the use of prednisone and/or azathioprine. The increase in A/H1N1-specific and A/H3N2-specific antibody titers after vaccination was lower in patients compared with control subjects.Conclusion. In addition to a decreased antibody response, cell-mediated responses to influenza vaccination are diminished in patients with SLE, which may reflect the effects of the concomitant use of immunosuppressive drugs. This may render these patients more susceptible to (complicated) influenza infections.

show abstract

“…Fifth, the phenotypes of cells responding in ELISpot assays are unknown. It can be speculated that NK cells are among the cells that have responded in our ELISpot assay (15).…”

Section: Discussionmentioning

confidence: 99%

“…After drying, spots were counted using an automated reader (automated ELISpot video analysis system; Sanquin, Amsterdam, The Netherlands). Results are referred to as IFN␥ spot-forming cells, because generation of IFN␥-producing CD4ϩ and CD8ϩ T cells as well as natural killer (NK) cells following WIV stimulation have been described (15).…”

Section: Methodsmentioning

confidence: 99%

Studies of cell‐mediated immune responses to influenza vaccination in systemic lupus erythematosus

Holvast¹,

Assen²,

Haan³

et al. 2009

Arthritis & Rheumatism

View full text Add to dashboard Cite

show abstract

“…NK and T cells are also important in generating protective responses to IIV, and influenza vaccination has proven to be a useful surrogate to evaluate the NK-and T-cell immune response to influenza virus in humans (33)(34)(35). This approach has not yet been applied to pregnant women.…”

Section: Significancementioning

confidence: 99%

“…To assess NK-and T-cell functional responses to influenza-virus infection, we modified an assay previously described by He et al and Long et al (33,35,36). PBMCs were incubated with influenza virus, resulting in infection of 60-70% of monocytes (Fig.…”

Section: Robust Inflammatory Responses To Influenza a Virus In Pregnamentioning

confidence: 99%

Enhanced natural killer-cell and T-cell responses to influenza A virus during pregnancy

Kay¹,

Fukuyama²,

Aziz

et al. 2014

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

View full text Add to dashboard Cite

Pregnant women experience increased morbidity and mortality after influenza infection, for reasons that are not understood. Although some data suggest that natural killer (NK)-and T-cell responses are suppressed during pregnancy, influenza-specific responses have not been previously evaluated. Thus, we analyzed the responses of women that were pregnant (n = 21) versus those that were not (n = 29) immediately before inactivated influenza vaccination (IIV), 7 d after vaccination, and 6 wk postpartum. Expression of CD107a (a marker of cytolysis) and production of IFN-γ and macrophage inflammatory protein (MIP) 1β were assessed by flow cytometry. Pregnant women had a significantly increased percentage of NK cells producing a MIP-1β response to pH1N1 virus compared with nonpregnant women pre-IIV [median, 6.66 vs. 0.90% (P = 0.0149)] and 7 d post-IIV [median, 11.23 vs. 2.81% (P = 0.004)], indicating a heightened chemokine response in pregnant women that was further enhanced by the vaccination. Pregnant women also exhibited significantly increased T-cell production of MIP-1β and polyfunctionality in NK and T cells to pH1N1 virus pre-and post-IIV. NK-and T-cell polyfunctionality was also enhanced in pregnant women in response to the H3N2 viral strain. In contrast, pregnant women had significantly reduced NK-and T-cell responses to phorbol 12-myristate 13-acetate and ionomycin. This type of stimulation led to the conclusion that NK-and T-cell responses during pregnancy are suppressed, but clearly this conclusion is not correct relative to the more biologically relevant assays described here. Robust cellular immune responses to influenza during pregnancy could drive pulmonary inflammation, explaining increased morbidity and mortality.

show abstract

“…Diminished CD161 expression has been observed on CMV-, HIV-or influenza-specific CD8 1 T cells [42], linked to increased CD8 1 T-cell functionality [43]. Likewise, CD161 lo NK cells may be less inhibited, allowing them to respond more aggressively within the LN during early HIV infection.…”

Section: Discussionmentioning

confidence: 99%

Early viral replication in lymph nodes provides HIV with a means by which to escape NK‐cell‐mediated control

et al. 2011

View full text Add to dashboard Cite

Acute HIV infection is marked by dramatic viral replication associated with preferential replication within secondary lymphoid tissues, such as lymph nodes (LNs), that is rapidly but incompletely contained to a viral setpoint. Accumulating evidence supports a role for natural killer (NK) cells in the early control of HIV infection; however, little is known about the location of their antiviral control. Given that HIV replicates profusely in LNs during early infection, we sought to define whether changes occurred in the NK cell infiltrate within these sites during the first year of HIV infection. Surprisingly, NK cell numbers and distribution were unaltered during early HIV infection. LN NK cells expressed decreased inhibitory receptors, were more highly activated, and expressed elevated TRAIL, potentially conferring a superior capacity for NK cells to become activated and control infection. Most noticeably, KIR+ NK cells were rarely detected in the LN during HIV infection, associated with diminished migratory capacity in the setting of reduced expression of CX3CR1 and CXCR1. Thus, incomplete control of HIV viral replication during early disease may be due to the inefficient recruitment of KIR+ NK cells to this vulnerable site, providing HIV a niche where it can replicate unabated by early NK‐cell‐mediated innate pressure.

show abstract

Elevated Frequency of Gamma Interferon-Producing NK Cells in Healthy Adults Vaccinated against Influenza Virus

Abstract: Recent studies indicate that innate immunity in influenza virus

Cited by 63 publications

References 31 publications

Studies of cell‐mediated immune responses to influenza vaccination in systemic lupus erythematosus

Studies of cell‐mediated immune responses to influenza vaccination in systemic lupus erythematosus

Enhanced natural killer-cell and T-cell responses to influenza A virus during pregnancy

Early viral replication in lymph nodes provides HIV with a means by which to escape NK‐cell‐mediated control

Contact Info

Product

Resources

About