title: CD4 T Helper Cells Instruct Lymphopenia-Induced Memory-Like CD8 T Cells for Control of Acute LCMV Infection.
abstract: Lymphopenic conditions lead to expansion of memory-like T cells (TML), which develop from naïve T cells by spontaneous proliferation. TMLcells are often increased in the elderly population, AIDS patients, and patients recovering from radio- or chemotherapy. At present, it is unclear whether TMLcells can efficiently respond to foreign antigen and participate in antiviral immunity. To address this question, we analyzed the immune response during acute low-dose infection with lymphocytic choriomeningitis virus-WE in T cell lymphopenic CD4Cre/R-diphtheria toxin alpha (DTA) mice in which most peripheral T cells show a TMLphenotype. On day 8 after infection, the total number of effector T cells and polyfunctional IFN-γ and TNF-α producing CD8 T cells were three- to fivefold reduced in CD4Cre/R-DTA mice as compared to controls. Viral clearance and the humoral immune response were severely impaired in CD4Cre/R-DTA mice although CTLs efficiently killed transferred target cellsin vivo. Transfer of naïve CD4 T cells but not anti-PD-L1 blockade restored the expansion of antigen-specific polyfunctional CD8 T cells and resulted in lower viral titers. This finding indicates that under lymphopenic conditions endogenous CD4 TMLcell lack the capacity to promote expansion of CTLs. However, CD8 TMLcells retain sufficient functional plasticity to participate in antiviral immunity in the presence of appropriate help by fully functional CD4 T cells. This capacity might be exploited to develop treatments for improvement of CD8 T cell functions under various clinical settings of lymphopenia.
authors.affiliation: Department of Infection Biology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) , Erlangen , Germany.
authors.forename: Michaela E R
authors.initials: ME
authors.lastname: Schmitt
authors.affiliation: Department of Infection Biology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) , Erlangen , Germany.
authors.forename: Selina
authors.initials: S
authors.lastname: Sitte
authors.affiliation: Department of Infection Biology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) , Erlangen , Germany.
authors.forename: David
authors.initials: D
authors.lastname: Voehringer
keywords: KLRG1; PD-1; lymphocytic choriomeningitis virus; lymphopenia; memory-like T cells