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Contents: 1. Introduction 2. Global field investigations on microplastic pollution in mussels 2.1 Selected species and geographic coverage 2.2 Characteristics of microplastic pollution 2.3 Methodological challenges 3. Laboratory exposures of microplastics in mussels 3.1 Uptake, accumulation and clearance of microplastics 3.2 Toxic effects of microplastics 3.3 Optimization of laboratory exposures 4. Scope of mussels as global bioindicators of microplastic 4.1 Advantages of utilizing mussel 4.2 Current regional and national proposals 4.3 Future developments

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When used as therapy for hematopoietic malignancies, allogeneic BM transplantation (BMT) relies on the graftversus-leukemia (GVL) effect to eradicate residual tumor cells through immunologic mechanisms. However, graft-versus-host disease (GVHD), which is initiated by alloreactive donor T cells that recognize mismatched major and/or minor histocompatibility antigens and cause severe damage to hematopoietic and epithelial tissues, is a potentially lethal complication of allogeneic BMT. To enhance the therapeutic potential of BMT, we sought to find therapeutic targets that could inhibit GVHD while preserving GVL and immune responses to infectious agents. We show here that T cell responses triggered in mice by either Listeria monocytogenes or administration of antigen and adjuvant were relatively well preserved in the absence of PKC isoform θ (PKCθ), a key regulator of TCR signaling. In contrast, PKCθ was required for alloreactivity and GVHD induction. Furthermore, absence of PKCθ raised the threshold for T cell activation, which selectively affected alloresponses. Most importantly, PKCθ-deficient T cells retained the ability to respond to virus infection and to induce GVL effect after BMT. These findings suggest PKCθ is a potentially unique therapeutic target required for GVHD induction but not for GVL or protective responses to infectious agents.

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