Platelet-mediated modulation of adaptive immunity: unique delivery of CD154 signal by platelet-derived membrane vesicles.

Although mounting evidence indicates that platelets participate in the modulation of both innate and adaptive immunity, the mechanisms by which platelets exert these effects have not been clearly defined. The study reported herein uses a previously documented adoptive transfer model to investigate the ability of platelet-derived membrane vesicles to communicate activation signals to the B-cell compartment. The findings demonstrate for the first time that platelet-derived membrane vesicles are sufficient to deliver CD154 to stimulate antigen-specific IgG production and modulate germinal center formation through cooperation with responses elicited by CD4(+) T cells.

Nuclear factor of activated T cells (NFAT) mediates CD154 expression in megakaryocytes.

Platelets are an abundant source of CD40 ligand (CD154), an immunomodulatory and proinflammatory molecule implicated in the onset and progression of several inflammatory diseases, including systemic lupus erythematosus (SLE), diabetes, and cardiovascular disease. Heretofore considered largely restricted to activated T cells, we initiated studies to investigate the source and regulation of platelet-associated CD154. We found that CD154 is abundantly expressed in platelet precursor cells, megakaryocytes.

The role of platelet CD154 in the modulation in adaptive immunity.

Platelets' primary role is hemostasis. However, a growing body of research has demonstrated that platelets are integral to the initiation of an inflammatory response and are potent effector cells of the innate immune response. Activated platelets express CD154, a molecule critical to adaptive immune responses, which has been implicated in platelet-mediated modulation of innate immune responses and inflammation.

The emerging role of platelets in adaptive immunity.

Platelets' foremost role in survival is hemostasis. However, a significant quantity of research has demonstrated that platelets are an integral part of inflammation and can also be potent effector cells of the innate immune response. CD154, a molecule of vital importance to adaptive immune responses, is expressed by activated platelets and has been implicated in platelet-mediated modulation of innate immunity and inflammatory disease states.

Telomerase activation in cervical keratinocytes containing stably replicating human papillomavirus type 16 episomes.

Retroviral transduction and expression of the human papillomavirus type 16 (HPV-16) E6 gene has been shown to activate telomerase in human cervical and foreskin keratinocytes. There still remains some controversy, however, as to whether expression of E6 in the context of the whole HPV-16 genome can activate telomerase. In this study, we have generated human cervical keratinocyte clones that contain stably replicating HPV-16 episomes.