Impaired T-cell responses to sphingosine-1-phosphate in HIV-1 infected lymph nodes

Impaired T-cell responses to sphingosine-1-phosphate in HIV-1 infected lymph nodes.

The determinants of HIV-1-associated lymphadenopathy are poorly understood. We hypothesized that lymphocytes could be sequestered in the HIV-1+ lymph node (LN) through impairments in sphingosine-1-phosphate (S1P) responsiveness. To test this hypothesis, we developed novel assays for S1P-induced Akt phosphorylation and actin polymerization. In the HIV-1+ LN, naïve CD4 T cells and central memory ...

The novel sphingosine-1-phosphate receptors antagonist AD2900 affects lymphocyte activation and inhibits T-cell entry into the lymph nodes

Sphingolipid derivatives play key roles in immune cell migration and function. Synthetic sphingolipid analogues are used as therapeutics to intervene various inflammatory and malignant conditions. We hypothesize that different analogs have different effects on immune cells and therefore can be used as treatment for specific diseases. This study examines the properties of the novel synthetic sph...

PD-1 regulates self-reactive CD8+ T cell responses to antigen in lymph nodes and tissues.

PD-1, an inhibitory receptor expressed on activated lymphocytes, regulates tolerance and autoimmunity. We tested the role of PD-1:PD-1 ligand (PD-L) interactions in cross-presentation and the generation and control of CD8(+) responses against self-Ag. Ag-naive PD-1(-/-) OVA-specific OT-I CD8(+) T cells exhibited exacerbated responses to cross-presented Ag in mice expressing soluble OVA under th...

Dendritic Cell Sphingosine 1-Phosphate

Local inactivation of sphingosine 1-phosphate in lymph nodes induces lymphopenia.

Sphingosine 1-phosphate (S1P) initiates T and B cell exit from lymphoid tissues by activating the S1P(1) receptor on lymphocytes. To define the mechanistic details of this ligand-receptor interaction, the biological activity of the S1P-blocking Ab Sphingomab was investigated. Treatment of mice with Sphingomab resulted in blood B and T cell lymphopenia. Although Sphingomab blocked S1P(1)-mediate...