The currently accepted model for superantigen (SAg) induced T cell activation suggests that SAg, without being processed, cross link both MHC class II, from Antigen Presenting Cells (APC), and V-, from T-cell receptor (TCR), initiating nonspecific T-cell activation. This T-cell proliferation induces a massive cytokine release associated with several human diseases. It is thought that murine CD...

Africans have elevated T cell activation compared to residents of Europe or the USA. Levels of T cell activation also correlate with disease progression in HIV-infected individuals. We sought to determine if treatment with antiretroviral therapy (ART) would reduce levels of T cell activation (CD38 and HLADR co-expression) in HIV-infected Ugandan children. The median CD8+ T cell activation level...

Priming of T cells in lymphoid tissues of HIV-infected individuals occurs in the presence of HIV-1. DC in this milieu activate T cells and disseminate HIV-1 to newly activated T cells, the outcome of which may have serious implications in the development of optimal antiviral responses. We investigated the effects of HIV-1 on DC-naïve T-cell interactions using an allogeneic in vitro system. Our ...

Naïve T cells continually recirculate between blood and secondary lymphoid organs, scanning dendritic cells (DC) for foreign antigen. Despite its importance for understanding how adaptive immune responses are efficiently initiated from rare precursors, a detailed quantitative analysis of this fundamental process has not been reported. Here we measure lymph node (LN) entry, transit, and exit rat...

Natural killer T (NKT) cells lie at the interface between the innate and adaptive immune systems and are important mediators of tumor immunosurveillance. This CD1d-restricted lymphoid population recognizes lipid antigen and can rapidly produce an array of cytokines and chemokines to modulate the host immune response. In tumor immunity, two NKT cell subsets (type I and type II) have contrasting ...

Congenital human cytomegalovirus (HCMV) infection is the major cause of birth defects and a precise definition of the HCMV-specific T-cell response in primary infection may help define reliable correlates of immune protection during pregnancy. In this study, a high throughput method was used to define the frequency of CD4+ and CD8+ T cells specific for four HCMV proteins in the naïve compartmen...

Recently, a new lineage of CD4+ T cells has been described in the mouse that specifically secretes IL-17 [T helper (Th) 17]. This discovery has led to a revision of the hypothesis that many autoimmune diseases are predominantly a Th1 phenomenon and may instead be critically dependent on the presence of Th17 cells. Murine Th17 cells differentiate from naïve T cell precursors in the presence of T...

We here describe novel aspects of CD8(+) and CD4(+) T cell subset interactions that may be clinically relevant and provide new tools for regulating the reconstitution of the peripheral CD8(+) T cell pools in immune-deficient states. We show that the reconstitution capacity of transferred isolated naïve CD8(+) T cells and their differentiation of effector functions is limited, but both dramatica...

Schistosome infection induces profound Th-biasing and immune suppression. Although much has been examined in mice, few studies have examined responses of naïve humans to schistosome antigens. In this study, we examined the response of naïve human peripheral blood mononuclear cells (nPBMC) to stimulation with Schistosoma mansoni soluble egg antigen (SEA) using a priming in vitro (PIV) assay. We ...

Differentiation of naïve CD4(+) T cells into effector (Th1, Th2, and Th17) and induced regulatory (iTreg) T cells requires lineage-specifying transcription factors and epigenetic modifications that allow appropriate repression or activation of gene transcription. The epigenetic silencing of cytokine genes is associated with the repressive H3K27 trimethylation mark, mediated by the Ezh2 or Ezh1 ...