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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Heterologous antigen encounters can induce transient T-memory contraction, allowing cytomegaloviral recrudescence in latently infected immunocompetent hosts. It is clear that latent CMV can reactivate in immunocompetent individuals, but the mechanism triggering such reactivations remains unclear. Recent clinical data suggest that reactivation can be subverted by CMV-specific T-memory. We therefore monitored CMV-specific T cells in immunocompetent mice with latent mCMV after a known reactivation trigger (LPS). LPS induced transient systemic contraction of mCMV-specific CD8 memory that was followed by transcriptional reactivation. Subsequent recovery of mCMV-specific T cells coincided with resumption of latency. These data suggest that bacterial antigen encounters can induce transient T-memory contraction, allowing viral recrudescence in hosts latently infected with herpes family viruses.

BACKGROUND:Damage-control laparotomy (DCL) has been used for traumatic and nontraumatic indications. We studied factors associated with delirium and outcome in this population. METHODS:We reviewed DCL patients at 15 centers for 2 years, including demographics, Charlson Comorbidity Index (CCI), diagnosis, operations, and outcomes. We compared 30-day mortality; renal failure requiring dialysis; number of takebacks; hospital, ventilator, and intensive care unit (ICU) days; and delirium-free and coma-free proportion of the first 30 ICU days (DF/CF-ICU-30) between trauma (T) and nontrauma (NT) patients. We performed linear regression for DF/CF-ICU-30, including age, sex, CCI, achievement of primary fascial closure (PFC), small and large bowel resection, bowel discontinuity, abdominal vascular procedures, and trauma as covariates. We performed one-way analysis of variance for DF/CF-ICU-30 against traumatic brain injury severity as measured by Abbreviated Injury Scale for the head. RESULTS:Among 554 DCL patients (25.8% NT), NT patients were older (58.9 ± 15.8 vs. 39.7 ± 17.0 years, p < 0.001), more female (45.5% vs. 22.1%, p < 0.001), and had higher CCI (4.7 ± 3.3 vs. 1.1 ± 2.2, p < 0.001). The number of takebacks (1.7 ± 2.6 vs. 1.5 ± 1.2), time to first takeback (32.0 hours), duration of bowel discontinuity (47.0 hours), and time to PFC were similar (63.2 hours, achieved in 73.5%). Nontrauma and T patients had similar ventilator, ICU, and hospital days and mortality (31.0% NT, 29.8% T). Nontrauma patients had higher rates of renal failure requiring dialysis (36.6% vs. 14.1%, p < 0.001) and postoperative abdominal sepsis (40.1% vs. 17.1%, p < 0.001). Trauma and NT patients had similar number of hours of sedative (89.9 vs. 65.5 hours, p = 0.064) and opioid infusions (106.9 vs. 96.7 hours, p = 0.514), but T had lower DF/CF-ICU-30 (51.1% vs. 73.7%, p = 0.029), indicating more delirium. Linear regression analysis indicated that Twas associated with a 32.1% decrease (95% CI, 14.6%-49.5%; p < 0.001) in DF/CF-ICU-30, while achieving PFC was associated with a 25.1% increase (95% CI, 10.2%-40.1%; p = 0.001) in DF/CFICU-30. Increasing Abbreviated Injury Scale for the head was associated with decreased DF/CF-ICU-30 by analysis of variance (p < 0.001). CONCLUSION:Nontrauma patients had higher incidence of postoperative abdominal sepsis and need for dialysis, while T was independently associated with increased delirium, perhaps because of traumatic brain injury.