Harnessing Treg Homeostasis to Optimize Posttransplant Immunity: Current Concepts and Future Perspectives

CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are functionally distinct subsets of mature T cells with broad suppressive activity and have been shown to play an important role in the establishment of immune tolerance after allogeneic hematopoietic stem cell transplantation (HSCT). Tregs exhibit an activated phenotype from the stage of emigration from the thymus and maintain continuous proliferation in the periphery. The distinctive feature in homeostasis enables Tregs to respond sensitively to small environmental changes and exert necessary and sufficient immune suppression; however, on the other hand, it also predisposes Tregs to be susceptible to apoptosis in the inflammatory condition post-transplant. Our studies have attempted to define the intrinsic and extrinsic factors affecting Treg homeostasis from the acute to chronic phases after allogeneic HSCT. We have found that altered cytokine environment in the prolonged post-HSCT lymphopenia or peri-transplant use of immune checkpoint inhibitors could hamper Treg reconstitution, leading to refractory graft-versus-host disease. Using murine models and clinical trials, we have also demonstrated that proper intervention with low-dose interleukin-2 or post-transplant cyclophosphamide could restore Treg homeostasis and further amplify the suppressive function after HSCT. The purpose of this review is to reconsider the distinctive characteristics of post-transplant Treg homeostasis and discuss how to harness Treg homeostasis to optimize posttransplant immunity for developing a safe and efficient therapeutic strategy.</p

The Lax pairs and conserved quantities of the delay Lotka-Volterra equation

The delay Lotka-Volterra equation is a delay-differential extension of the well known Lotka-Volterra equation, and is known to have N-soliton solutions. In this paper, Backlund transformations, Lax pairs and infinite conserved quantities of the delay Lotka-Volterra equation and its discrete analogue are constructed. The conserved quantities of the delay Lotka-Volterra equation turn out to be complicated and described by using the time-ordered product of linear operators.Comment: 11 page

Sensitive Photodynamic Detection of Adult T-cell Leukemia/Lymphoma and Specific Leukemic Cell Death Induced by Photodynamic Therapy: Current Status in Hematopoietic Malignancies

Adult T-cell leukemia/lymphoma (ATL), an aggressive type of T-cell malignancy, is caused by the human T-cell leukemia virus type I (HTLV-1) infections. The outcomes, following therapeutic interventions for ATL, have not been satisfactory. Photodynamic therapy (PDT) exerts selective cytotoxic activity against malignant cells, as it is considered a minimally invasive therapeutic procedure. In PDT, photosensitizing agent administration is followed by irradiation at an absorbance wavelength of the sensitizer in the presence of oxygen, with ultimate direct tumor cell death, microvasculature injury, and induced local inflammatory reaction. This review provides an overview of the present status and state-of-the-art ATL treatments. It also focuses on the photodynamic detection (PDD) of hematopoietic malignancies and the recent progress of 5-Aminolevulinic acid (ALA)-PDT/PDD, which can efficiently induce ATL leukemic cell-specific death with minor influence on normal lymphocytes. Further consideration of the ALA-PDT/PDD system along with the circulatory system regarding the clinical application in ATL and others will be discussed. ALA-PDT/PDD can be promising as a novel treatment modality that overcomes unmet medical needs with the optimization of PDT parameters to increase the effectiveness of the tumor-killing activity and enhance the innate and adaptive anti-tumor immune responses by the optimized immunogenic cell death

A delay analogue of the box and ball system arising from the ultra-discretization of the delay discrete Lotka-Volterra equation

A delay analogue of the box and ball system (BBS) is presented. This new soliton cellular automaton is constructed by the ultra-discretization of the delay discrete Lotka-Volterra equation, which is an integrable delay analogue of the discrete Lotka-Volterra equation. This delay BBS requires multiple time initial states for time evolution, thus it has various types of soliton patterns. Soliton patterns generated by the delay BBS are classified into normal solitons and abnormal solitons. Normal solitons can be discussed analytically, while abnormal solitons show various phenomena which are not explained easily. Finally, we show that the delay BBS is equivalent to the BBS with K kinds of balls if we consider only normal solitons