T cell stimulation usually requires direct contact with viable antigen-presenting cells (APCs). However, we show here that small exosome-like membrane vesicles shed from APCs can be recognized by naïve CD8+ T cells in the absence of viable APCs. T cell antigen receptor-dependent binding of vesicles by CD8+ cells is MHC class I/peptide-specific and requires that the vesicles coexpress intercellular adhesion molecule 1 (ICAM-1, CD54), although not B7 (B7-1). In the absence of B7, T cell binding of vesicles is nonimmunogenic. By contrast, vesicles expressing both ICAM-1 and B7 are strongly immunogenic and cause purified APC-depleted CD8+ cells to mount peptide-specific proliferative responses and differentiate into effector cells.

Immunologists gather at Asilomar each January in a pleasant and informal setting to discuss recent findings on the development and regulation of immune responses.

The predisposition of nonobese diabetic (NOD) mice to develop autoimmune disease is usually attributed to defects in peripheral tolerance mechanisms. Here, evidence is presented that NOD mice display a defect in central tolerance (negative selection) of thymocytes. Impaired central tolerance in NOD mice was most prominent in a population of semi-mature thymocytes found in the medulla. The defect was apparent in vivo as well as in vitro, was independent of IAg7 expression and affected both Fas-dependent and Fas-independent pathways of apoptosis; for Fas-dependent apoptosis, the defective tolerance of NOD thymocytes correlated with the strong T cell receptor−mediated up-regulation of caspase 8−homologous FLICE (Fas-associated death-domain-like interleukin 1−converting enzyme)-inhibitory protein. In light of these findings, disease onset in NOD mice may reflect defects in central as well as peripheral tolerance.

Typical T cells are long-lived resting cells. Despite their quiescent appearance, there is increasing evidence that T cells are subjected to continuous stimulation through contact with various stimuli, notably by self peptide/MHC complexes and cytokines. These stimuli keep T cells alive and also cause intermittent entry into cell cycle.