Presentation Highlights

During Wednesday’s State-of-the-Art Session, Platelets Beyond Thrombosis, John W. Semple, Ph.D. highlighted the attributes of platelets and their precursor cells, megakaryocytes (MK) in their ability to modulate immunity, particularly via their major histocompatibility complex (MHC) class I molecules:

  • Platelets contain several potent immunoregulatory molecules including TLR and CD40L.
  • Resting platelet MHC class I molecules may evoke a direct faulty interaction with CD8+ T cell (CTL) receptors.
  • Activated platelets express conformationally intact MHC class I molecules from an internal alpha-granule pool; these allow activated platelets to present antigens to CD8+ T cells.
  • This is an important mechanism of immunoregulation, particularly in immune thrombocytopenia.

Current data support the novel concept that platelets and MKs may be responsible for directly controlling adaptive immune functions.


Platelets are the primary cellular mediators of hemostasis and this function intimately acquaints them with a variety of inflammatory processes. For example, when aggregated on damaged vessel walls, activated platelets can capture circulating leukocytes and attract them to inflamed tissue.

As early as the 1970s, researchers showed that platelets play an active role in the regulation of innate and adaptive immune responses. Platelets secrete several pro- and anti-inflammatory chemokines/cytokines that can affect local innate immune responses by attracting neutrophils to sites of inflammation, express the entire family of Toll-like receptors (TLR) and act as primary circulating sentinel cells, first encountering blood-borne bacterial products for presentation and activation of the innate immune system, and directly regulate adaptive humoral immune responses via their expression and secretion of CD40/CD40L molecules.

In addition, resting platelets express class I molecules encoded by MHC. Resting platelet MHC class I molecules are primarily adsorbed from plasma and consist of truncated heavy chains that are unstable; more than 80% can be eluted from the platelet surface by chloroquine diphosphate or platelet storage, without affecting platelet membrane integrity. Because of these features, resting platelet MHC class I molecules may evoke a direct faulty interaction with CD8+ T cell receptors thereby anergizing this adaptive immune effector cell. Support for this comes from studies that show that platelet MHC class I molecules cannot activate cytotoxic T lymphocytes (CTLs) on their own and that allogeneic platelet transfusions can significantly enhance donor-specific skin graft survival, an adaptive immune process that is exclusively mediated by CTLs.

In contrast, however, it has recently been demonstrated that activated platelets express conformationally intact MHC class I molecules from an internal alpha granule pool; these allow activated platelets to actually present antigens to CD8+ T cells. These results have important implications for immunoregulation, particularly in the autoimmune platelet disorder, immune thrombocytopenia.

Semple highlighted the attributes of platelet and MK MHC class I molecules and discussed how these molecules can significantly regulate adaptive immune responses in both a suppressive and stimulatory manner.

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