Regulatory T-Cell Activity But Not Conventional HIV-Specific T-Cell Responses Are Associated With Protection From HIV-1 Infection

Pattacini, Laura; Baeten, Jared M.; Thomas, Katherine K.; Fluharty, Tayler R.; Murnane, Pamela M.; Donnell, Deborah; Bukusi, Elizabeth A.; Ronald, Allan R.; Mugo, Nelly; Lingappa, Jairam R.; Celum, Connie; McElrath, M. Juliana; Lund, Jennifer M.

doi:10.1097/qai.0000000000000919

Cited by 16 publications

(11 citation statements)

References 54 publications

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“…In addition, we found that an increased frequency of Tregs with a unique suppressive profile correlated with protection ( Figure 2), which supports the notion that balance between active immunity and suppression is likely critical to spare the host from severe disease after infection. We have previously found that Tregs can play a role in protection from human immunodeficiency virus infection through analysis of a case-control cohort [39], and, in addition, there is precedent for Tregs playing a role in protection from immunopathology after infection [40][41][42]. Furthermore, it has previously been shown that Treg activity is required during viral infections to allow for appropriate generation and migration of immune effector cells to the site of infection [43][44][45].…”

Section: Discussionmentioning

confidence: 99%

Immune predictors of mortality following RNA virus infection

Graham

Swarts

Menachery

et al. 2019

The Journal of Infectious Diseases

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Background Virus infections result in a range of clinical outcomes for the host, from asymptomatic to severe or even lethal disease. Despite global efforts to prevent and treat virus infections to limit morbidity and mortality, the continued emergence and re-emergence of new outbreaks as well as common infections such as influenza persist as a health threat. Challenges to the prevention of severe disease after virus infection include both a paucity of protective vaccines, as well as the early identification of individuals with the highest risk that may require supportive treatment. Methods We completed a screen of mice from the Collaborative Cross (CC) that we infected with influenza, SARS-coronavirus, and West Nile virus. Results CC mice exhibited a range of disease manifestations upon infections, and we used this natural variation to identify strains with mortality following infection and strains exhibiting no mortality. We then used comprehensive pre-infection immunophenotyping to identify global baseline immune correlates of protection from mortality to virus infection. Conclusions These data suggest that immune phenotypes might be leveraged to identify humans at highest risk of adverse clinical outcomes upon infection, who may most benefit from intensive clinical interventions, in addition to providing insight for rational vaccine design.

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Section: Discussionmentioning

confidence: 99%

Immune predictors of mortality following RNA virus infection

Graham

Swarts

Menachery

et al. 2019

The Journal of Infectious Diseases

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“…Healthy heterosexuals engaged in vaginal intercourse with an HIV-positive partner [ 107 ], have very low rates of seroconversion (1 in 3000 to 1 in 8000). HIV appears to require already impaired immunity or various cofactors to overcome immunological tolerance to it in order to induce active disease [ 15 , 81 , 108 , 109 , 110 , 111 ]. Such pre-conditions would be consistent with HIV being a commensal, or near-commensal, organism for human beings.…”

Section: Discussionmentioning

confidence: 99%

Human Immunodeficiency Virus Proteins Mimic Human T Cell Receptors Inducing Cross-Reactive Antibodies

Root‐Bernstein

2017

IJMS

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“…Immediately following staining, samples were analyzed using a LSRII flow cytometer (BD Biosciences, CA, USA) with FlowJo software (Tree Star OR). Tregs were considered to be CD3+CD4+CD25hiFoxp3+CD127dim cells, as published previously ( Pattacini et al., 2016 ).…”

Section: Methodsmentioning

confidence: 99%

Extensive Homeostatic T Cell Phenotypic Variation within the Collaborative Cross

Graham¹,

Swarts²,

Mooney³

et al. 2017

Cell Reports

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Summary The Collaborative Cross (CC) is a panel of reproducible recombinant inbred mouse strains with high levels of standing genetic variation, thereby affording unprecedented opportunity to perform experiments in a small animal model containing controlled genetic diversity while allowing for genetic replicates. Here, we advance the utility of this unique mouse resource for immunology research, as it allows for both examination and genetic dissection of mechanisms behind adaptive immune states in mice with distinct and defined genetic makeups. This approach is founded on quantitative trait locus mapping: identifying genetically variant genome regions associated with phenotypic variance in traits-of-interest. Furthermore, the CC can be utilized for mouse model development; distinct strains have unique immunophenotypes and immune properties, making them suitable for research on particular diseases and infections. Here, we describe variation in cellular immune phenotypes across F1 crosses of CC strains, and reveal quantitative trait loci responsible for several immune phenotypes.

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Regulatory T-Cell Activity But Not Conventional HIV-Specific T-Cell Responses Are Associated With Protection From HIV-1 Infection

Cited by 16 publications

References 54 publications

Immune predictors of mortality following RNA virus infection

Immune predictors of mortality following RNA virus infection

Human Immunodeficiency Virus Proteins Mimic Human T Cell Receptors Inducing Cross-Reactive Antibodies

Extensive Homeostatic T Cell Phenotypic Variation within the Collaborative Cross

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