PD-1-dependent mechanisms maintain peripheral tolerance of donor-reactive CD8+ T cells to transplanted tissue

Peripheral mechanisms of self-tolerance often depend on the quiescent state of the immune system. To what degree such mechanisms can be engaged in the enhancement of allograft survival is unclear. To examine the role of the PD-1 pathway in the maintenance of graft survival following blockade of costimulatory pathways, we used a single-Ag mismatch model of graft rejection where we could track the donor-specific cells as they developed endogenously and emerged from the thymus. We found that graft-specific T cells arising under physiologic developmental conditions at low frequency were actively deleted at the time of transplantation under combined CD28/CD40L blockade. However, this deletion was incomplete, and donor-specific cells that failed to undergo deletion up-regulated expression of PD-1. Furthermore, blockade of PD-1 signaling on these cells via in vivo treatment with anti-PD-1 mAb resulted in rapid expansion of donor-specific T cells and graft loss. These results suggest that the PD-1 pathway was engaged in the continued regulation of the low-frequency graft-specific immune response and thus in maintenance of graft survival.     

SHW1, a common regulator of abscisic acid (ABA) and light signaling pathways

In our recent paper in Plant Physiology, we have reported the identification and functional characterization of a unique regulator, SHW1, a serine-arginine-aspartate rich protein in Arabidopsis seedling development.¹ Genetic and molecular analyses have revealed that SHW1 functions in an independent and interdependent manner with COP1, and differentially regulates photomorphogenic growth and light regulated gene expression. Here, we show the involvement of photoreceptors in the function of SHW1. Our results have further revealed that SHW1 is a common regulator of light and ABA signaling pathways. These results along with some data described in Plant Physiology paper have been discussed here in a broader perspective.Key words: light signaling, photomorphogenesis, SHW1, COP1, ABA responsePlants are exposed to various intensities and wavelengths of light with a specific wavelength of light being predominant at a particular daytime. For example, plants are exposed to varied intensities of light in the morning and noon, or far-red light being predominant in the twilight. However, plants have also evolved to respond to and subsequently tackle such variations in light quality or quantity by multiple modes of actions. One such mode of action might be to employ multiple negative regulatory proteins that function as filtering units to light intensity. These negative regulators could be operative in a specific wavelength of light or in a broad spectrum of light². Identification and functional characterization of several negative regulators, including SHW1, of photomorphogenic growth support such notion. SHW1 does not seem to have a homologue in animal system or in lower eukaryotes, and thereby has evolved as a plant specific gene. When seedlings are exposed to light after reaching the soil surface, it is important to protect the emerging cotyledons from high intensity light that otherwise might get bleached and subsequently die. SHW1 is expressed in germinating seeds to flowering plants, and it is predominantly expressed in the photosynthetically active tissues.¹ Therefore, SHW1 might function as a filtering unit not only in the case of emerging seedlings in the soil but also in the adult plants during dark to light transition.