Rapid effector function of memory CD8+ T cells requires an immediate-early glycolytic switch.

Antigen-experienced memory T cells acquire effector function with innate-like kinetics; however, the metabolic requirements of these cells are unknown. Here we show that rapid interferon-γ (IFN-γ) production of effector memory (EM) CD8(+) T cells, activated through stimulation mediated by the T cell antigen receptor (TCR) and the costimulatory receptor CD28 or through cognate interactions, was linked to increased glycolytic flux. EM CD8(+) T cells exhibited more glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity at early time points, before proliferation commenced, than did naive cells activated under similar conditions.

Epstein-Barr virus negativity among individuals older than 60 years is associated with HLA-C and HLA-Bw4 variants and tonsillectomy.

Epstein-Barr virus (EBV) infects ≈ 95% of the adult population. The factors that confer protection in the remaining ≈ 5% remain unknown. In an exploratory study, we assessed immunogenetic factors and tonsillectomy in a cohort of 17 EBV-negative and 39 EBV-positive healthy individuals aged >60 years.

Antigen-specific adaptive immune responses in fingolimod-treated multiple sclerosis patients.

T cells exit secondary lymphoid organs along a sphingosine1-phosphate (S1P) gradient and, accordingly, are reduced in blood upon fingolimod-mediated S1P-receptor (S1PR)-blockade. Serving as a model of adaptive immunity, we characterized cellular and humoral immune responses to influenza vaccine in fingolimod-treated patients with multiple sclerosis (MS) and in untreated healthy controls. Although the mode of action of fingolimod might predict reduced immunity, vaccine-triggered T cells accumulated normally in blood despite efficient S1PR-blockade.

Virosomal influenza-vaccine induced immunity in HIV-infected individuals with high versus low CD4+ T-cell counts: clues towards a rational vaccination strategy.

In a prospective influenza-vaccination trial we show that HIV-infected individuals with CD4 T-cell counts less than 350 microl were distinct from HIV-infected individuals with more than 350 CD4 T-cell counts/microl, and from HIV-negative individuals, in that an influenza-specific immunoglobulin M-response was absent and expansion of interferon-gamma-secreting CD4 T cells was impaired. By contrast, immunoglobulin G-responses were induced in all study groups. These data suggest that establishing broad influenza-specific (immunoglobulin G) B-cell memory prior to severe immunodeficiency is important.

NKG2D ligand expression in AML increases in response to HDAC inhibitor valproic acid and contributes to allorecognition by NK-cell lines with single KIR-HLA class I specificities.

This study exploited alloreactivity of natural killer (NK) cells for augmenting the recognition of human acute myeloid leukemia (AML). To circumvent the inhibitory effect of killer immunoglobulin receptor (KIR) signaling, we generated NK-cell lines with single KIR specificities for major human leukocyte antigen (HLA) class I allotypes. We demonstrated efficient cytolysis of KIR-HLA class I-mismatched primary AML blasts even at low effector-to-target ratios.