Immunology of Infectious Disease News Volume 3.37 | Sep 30 2015

The Interleukin-2-mTORc1 Kinase Axis Defines the Signaling, Differentiation, and Metabolism of T Helper 1 and Follicular B Helper T Cells
Scientists found that follicular B helper T cells exhibited less proliferation, glycolysis, and mitochondrial respiration, accompanied by reduced mTOR kinase activity compared to T helper 1 cells in response to acute viral infection. [Immunity] Abstract | Graphical Abstract

Functional Classification of Memory CD8⁺ T Cells by CX₃CR1 Expression
Researchers demonstrated that the fractalkine-receptor/CX₃CR1 distinguishes memory CD8⁺ T cells with cytotoxic effector function from those with proliferative capacity, independent of tissue-homing properties. Virus-specific CX₃CR1⁺ memory CD8⁺ T cells are scarce during chronic infection in humans and mice but increase when infection is controlled spontaneously or by therapeutic intervention. [Nat Commun] Full Article

Tissue Distribution of Memory T and B Cells in Rhesus Monkeys following Influenza A Infection
Using a nonhuman primate model, researchers revealed substantial induction of local T and B cell responses following the 2009 pandemic H1N1 infection. They identified a subset of influenza-specific lung memory T cells characterized as tissue-resident memory T cells in rhesus monkeys. [J Immunol] Abstract | Full Article

HIV

Dual-Affinity Re-Targeting Proteins Direct T Cell–Mediated Cytolysis of Latently HIV-Infected Cells
Researchers employed Dual-Affinity Re-Targeting (DART) proteins, which are bispecific, antibody-based molecules that can bind 2 distinct cell-surface molecules simultaneously. They designed DARTs with a monovalent HIV-1 envelope-binding arm that was derived from broadly binding, antibody-dependent cellular cytotoxicity–mediating antibodies known to bind to HIV-infected target cells coupled to a monovalent CD3 binding arm designed to engage cytolytic effector T cells. [J Clin Invest] Full Article | Press Release

Role of T-Cell Reconstitution in HIV-1 Antiretroviral Therapy-Induced Bone Loss
Scientists hypothesized that skeletal deterioration following HIV disease reversal with antiretroviral therapy (ART) may be related to T-cell repopulation and/or immune reconstitution. They transplanted T cells into immunocompromised mice to mimic ART-induced T-cell expansion. T-cell reconstitution elicited RANKL and TNFα production by B cells and/or T cells, accompanied by enhanced bone resorption and bone mineral density loss. [Nat Commun] Abstract

Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection
Investigators first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. They detected cell-associated SIV DNA and RNA in the stromal vascular fraction and in sorted CD4⁺ T cells and macrophages from adipose tissue. [PLoS Pathog] Full Article | Press Release

Persistent Simian Immunodeficiency Virus Infection Causes Ultimate Depletion of Follicular Th Cells in AIDS
Although CD4⁺ T follicular helper (Tfh) cells are reported to accumulate in HIV or SIV infection, investigators found that germinal center Tfh cells did not consistently accumulate in chronically SIV-infected rhesus macaques compared with those infected with less pathogenic simian HIV, vaccinated and SIVmac-challenged, or SIVmac-infected Mamu-A*01+ macaques, all of which are associated with some control of virus replication and slower disease progression. [J Immunol] Abstract

Effect of Depot Medoxyprogesterone Acetate on Immune Functions and Inflammatory Markers of HIV-Infected Women
Researchers evaluated the effect of a single depot medroxyprogesterone acetate injection on cell-mediated immunity, T cell activation, regulation and inflammation in HIV-infected women on cART. [J Acquir Immune Defic Syndr] Abstract

Multidimensional Clusters of CD4⁺ T Cell Dysfunction Are Primarily Associated with the CD4/CD8 Ratio in Chronic HIV Infection
Multi-parametric flow cytometry was used to investigate immune activation, exhaustion, and senescence of diverse maturation phenotypes of CD4⁺ T cells. Multiple correlation analyses between laboratory parameters and pathological CD4⁺ clusters revealed that the CD4/CD8 ratio was the preeminent surrogate marker of CD4⁺ T cells dysfunction using all three methods. [PLoS One] Full Article

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NewLink Genetics Receives $8.1 Million Award from DTRA to Advance Ebola Vaccine
NewLink Genetics Corporation announced that the Defense Threat Reduction Agency (DTRA) of the United States Department of Defense has awarded a subsidiary of NewLink Genetics an $8.1 million base contract with future options totaling $5.2 million to support various development activities of the investigational rVSV-ZEBOV (Ebola) vaccine candidate. [NewLink Genetics Corporation] Press Release

$3 Million Funds Research to Develop New HIV Vaccine Strategies
Infectious disease researchers at the University of Rochester School of Medicine and Dentistry will use $3.1 million from the National Institutes of Health to find new ways to develop a vaccine to prevent HIV. [University of Rochester Medical Center] Press Release

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