The role of astrocytes in the immune-mediated inflammatory response in the brain is more prominent than previously thought. Astrocytes become reactive in response to neuro-inflammatory stimuli through multiple pathways, contributing significantly to the machinery that modifies the parenchymal environment. In particular, astrocytic signaling induces the establishment of critical relationships wi...

Immunological synapses are organized cell-cell junctions between T lymphocytes and APCs composed of an adhesion ring, the peripheral supramolecular activation cluster (pSMAC), and a central T cell receptor cluster, the central supramolecular activation cluster (cSMAC). In CD8(+) cytotoxic T lymphocytes, the immunological synapse is thought to facilitate specific killing by confining cytotoxic a...

The binding of costimulatory ligand CD80 to CD28 or CTLA-4 on T cells plays an important role in the regulation of the T cell response. We have examined the role of the cytoplasmic domain of CD80 in murine T cell costimulation and its organization in the immunological synapse (IS). Removal of CD80 cytoplasmic tail decreased its effectiveness in costimulating T cell proliferative response and ea...

Natural killer (NK) cells are innate immune effectors that eliminate diseased and tumorigenic targets through the directed secretion of specialized secretory lysosomes, termed lytic granules. This directed secretion is triggered following the formation of an immunological synapse (IS), which is characterized by actin re-modeling and receptor organization at the interface between the NK cell and...

The interaction of T cells and antigen-presenting cells is central to adaptive immunity and involves the formation of immunological synapses in many cases. The surface molecules of the cells form a characteristic spatial pattern whose formation mechanisms and function are largely unknown. We perform computer simulations of recent experiments on geometrically repatterned immunological synapses a...

Similar to stem cells, naïve T cells undergo asymmetric division following activation. While asymmetric division of T cells has been shown to be an important mechanism for the generation of lymphocyte fate diversity during immune responses, key factors that influence whether T cells will undergo symmetric or asymmetric divisions are not completely understood. Here, we utilized immunological syn...

Adenosine deaminase (ADA), a protein whose deficit leads to severe combined immunodeficiency, binds to the cell surface by means of either CD26, A(1) adenosine receptors, or A(2B) adenosine receptors. The physiological role of these interactions is not well understood. Our results show that by a 3-fold reduction in the EC(50) for the antigen, ADA potentiated T cell proliferation in autologous c...

The addition of recombinant IL-12p75 (rIL-12p75) to naïve T cells promotes their differentiation toward a TH I-type cytokine patten by inducing IFN-y production. Therefore, it has been postulated that during the cognate interaction and formation of the immunological synapse between antigen-bearing DC and antigen-specific T cells, secretion of IFN-y and IL-12p75 would positively regulate each ot...

A major challenge in the development of a cure for human immunodeficiency virus (HIV) has been the incomplete understanding of the basic mechanisms underlying HIV persistence during antiretroviral therapy. It is now realized that the establishment of a latently infected reservoir refractory to immune system recognition has thus far hindered eradication efforts. Recent investigation into the inn...