Transient CD8-memory contraction: a potential contributor to latent cytomegalovirus reactivation

Campbell, Jonathan E.; Trgovcich, Joanne; Kincaid, Michelle; Zimmerman, Peter D.; Klenerman, Paul; Sims, Stuart; Cook, Charles H.

doi:10.1189/jlb.1211635

Cited by 12 publications

(14 citation statements)

References 40 publications

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“…All but two patients displaying undetectable CMV‐specific T‐cell responses at baseline had septic shock at intensive care unit admission. Recent data demonstrating a transient CMV‐specific CD8 + T‐cell memory contraction in mice infected with mCMV and treated with bacterial lipopolysaccharide may help to explain our data [Campbell et al, ]. This phenomenon, nevertheless, does not seem to occur systematically in humans, as a number of patients in the current series who had or went on to develop severe sepsis or septic shock were able to maintain detectable CMV‐specific T‐cell responses throughout the study period.…”

Section: Discussionsupporting

confidence: 49%

Evaluation of cytomegalovirus (CMV)-specific t-cell immunity for the assessment of the risk of active CMV infection in non-immunosuppressed surgical and trauma intensive care unit patients

et al. 2013

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The current study was designed to assess the predictive value of the evaluation of cytomegalovirus (CMV)-specific T-cell immunity early following admission to the intensive care unit for inferring the risk of active CMV infection in non-immunosuppressed surgical and trauma patients. A total of 31 CMV-seropositive patients were included. Patients were screened for the presence of CMV DNA in plasma and in tracheal aspirates by real-time PCR. Enumeration of CMV pp65 and IE-1-specific IFN-γ CD8(+) and CD4(+) T cells was performed by flow cytometry for intracellular cytokine staining. Virological and immunological monitoring was conducted once or twice a week. Active CMV infection occurred in 17 out of 31 patients. Undetectable levels of pp65 and IE-1-specific IFN-γ CD8(+) and CD4(+) T-cell subsets cells were observed in 10 patients who developed active CMV infection and in one who did not (at a median of 2 days following ICU admission). Peak CMV DNA loads in both tracheal aspirates and plasma were substantially higher (P = 0.018 and P = 0.091, respectively) in patients with undetectable IFN-γ T-cell responses than in patients with detectable responses. The expansion of both CMV-specific T-cell subsets following detection of active CMV infection was demonstrated in 9 out of 14 patients with active CMV infection. In conclusion, the evaluation of CMV pp65 and IE-1-specific IFN-γ-producing CD8(+) and CD4(+) T cells early following ICU admission may allow the identification of patients most at risk of either having or developing an episode of active CMV infection, particularly those associated with high-level virus replication.

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Section: Discussionsupporting

confidence: 49%

Evaluation of cytomegalovirus (CMV)-specific t-cell immunity for the assessment of the risk of active CMV infection in non-immunosuppressed surgical and trauma intensive care unit patients

et al. 2013

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“…Second, reactivation is not prerequisite, as viruses containing mCMV epitopes but incapable of replication have been shown to cause T-memory inflation [15, 64]. Finally, the current report suggests that a single strong reactivation stimulus (LPS) that has been previously shown to cause consistent transcriptional reactivation [44, 45] is insufficient to cause memory inflation.…”

Section: Discussionmentioning

confidence: 80%

“…To test this hypothesis, we used mice latently infected with low titer (10 2 pfu) Smith mCMV. After confirmation of partial memory inflation 16–20 weeks after infection, mice were treated with sub-lethal LPS, a reactivation stimulus previously shown to consistently cause transcriptional reactivation, [44, 45] or saline control. LPS stimulation did not cause any significant difference in MCMV-specific T-cells ( Fig 6A ).…”

Section: Resultsmentioning

confidence: 99%

Cytomegalovirus Reinfections Stimulate CD8 T-Memory Inflation

et al. 2016

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Cytomegalovirus (CMV) has been shown to induce large populations of CD8 T-effector memory cells that unlike central memory persist in large quantities following infection, a phenomenon commonly termed “memory inflation”. Although murine models to date have shown very large and persistent CMV-specific T-cell expansions following infection, there is considerable variability in CMV-specific T-memory responses in humans. Historically such memory inflation in humans has been assumed a consequence of reactivation events during the life of the host. Because basic information about CMV infection/re-infection and reactivation in immune competent humans is not available, we used a murine model to test how primary infection, reinfection, and reactivation stimuli influence memory inflation. We show that low titer infections induce “partial” memory inflation of both mCMV specific CD8 T-cells and antibody. We show further that reinfection with different strains can boost partial memory inflation. Finally, we show preliminary results suggesting that a single strong reactivation stimulus does not stimulate memory inflation. Altogether, our results suggest that while high titer primary infections can induce memory inflation, reinfections during the life of a host may be more important than previously appreciated.

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“…Unlike HHV with cutaneous manifestations, such as HSV-1/2 and VZV, whose reactivation episodes are obvious, it is unknown how frequently the other HHV may reactivate in immune competent hosts. It does seem clear, however, that transient compromise in host immunity will allow transcriptional reactivation of these viruses (58, 59). For the purposes of this article, we will define immune competent hosts as those not undergoing canonical immune suppression or have disease related immune compromise (such as AIDS), understanding that following surgery, trauma or critical illness there may very well be transient compromise in host immunity (60).…”

Section: Virusesmentioning

confidence: 99%

“…These reactivation events can lead to live virus shed in the blood and pulmonary secretions of affected hosts (115, 116). It seems likely that these reactivation events are consequent to inflammatory insults that trigger release of cytokines, epigenetic deregulation of viral genomes, and possibly immune compromise (58, 67, 117–119). It remains unclear, however, whether CMV is a true pathogen or merely an indicator of severity of illness.…”

Section: Virusesmentioning

confidence: 99%

Resistant Pathogens, Fungi, and Viruses

Guidry

Mansfield

Sawyer

et al. 2014

Surgical Clinics of North America

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The first reports of antibiotic pathogens occurred a few short years after the introduction of these powerful new agents, heralding a new kind of war between medicine and pathogens. Although originally described in Staphylococcus aureus, resistance among bacteria has now become a grim race to determine which classes of bacteria will become more resistant, pitting the Gram positive staphylococci, enterococci, and streptococci against the increasingly resistant Gram negative pathogens, e. g., carbapenemase-resistant enterobacteriaceae. In addition, the availability of antibacterial agents has allowed the development of whole new kinds of diseases caused by non-bacterial pathogens, related largely to fungi that are inherently resistant to antibacterials. All of these organisms are becoming more prevalent and, ultimately, more clinically relevant for surgeons. It is ironic that despite their ubiquity in our communities, there is seldom a second thought given to viral infections in patients with surgical illness. The extent of most surgeon’s interest in viral infections ends with hepatitis and HIV, no doubt related to transmissibility as well as the implications that these viruses might have in a patient’s hepatic or immune functions. There are chapters and even textbooks written about these viruses so these will not be considered here. Instead, we will present the growing body of knowledge of the herpes family viruses and their occurrence and consequences in patients with concomitant surgical disease or critical illness. We have also chosen to focus this chapter on previously immune competent patients, as the impact of herpes family viruses in immunosuppressed patients such as transplant or AIDS patients has received thorough treatment elsewhere.

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Transient CD8-memory contraction: a potential contributor to latent cytomegalovirus reactivation

Cited by 12 publications

References 40 publications

Evaluation of cytomegalovirus (CMV)-specific t-cell immunity for the assessment of the risk of active CMV infection in non-immunosuppressed surgical and trauma intensive care unit patients

Evaluation of cytomegalovirus (CMV)-specific t-cell immunity for the assessment of the risk of active CMV infection in non-immunosuppressed surgical and trauma intensive care unit patients

Cytomegalovirus Reinfections Stimulate CD8 T-Memory Inflation

Resistant Pathogens, Fungi, and Viruses

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