Most of the current cell-based immunotherapy protocols concentrate on immune stimulatory effects against certain pathogenic insults, such as cancer. In this article, a potential cell-based immunotherapeutic strategy to induce immune tolerance by infusion of apoptotic leukocytes is presented in conjunction with a review of newly understood mechanisms of action of photopheresis and relevant information about allogeneic transfusion-related immunomodulation. The scientific rationale is discussed by examining our understanding of the role of apoptosis in self-antigen tolerance, the interaction between apoptotic bodies and antigen-presenting cells, and the subsequent induction of T regulatory cells and clonal deletion of effector T cells. Previous data on transfusion-related immunomodulation are assembled to examine a possible link between the immunosuppressive effects obtained from photopheresis and those seen post allogeneic blood transfusion. Accumulating evidence appears to support the hypothesis that photopheresis and allogeneic blood transfusion may share a mechanism of action for the induction of immunosuppression, which suggests the potential of eliciting selective immune tolerance by giving the recipient a bolus of apoptotic cells. Such immunotherapy interventions could bring significant clinical benefit to patients undergoing transplant rejection or autoimmune-related disorders and deserve further investigation as well as validation studies.
[Show abstract][Hide abstract] ABSTRACT: Nonstationary signals are partitioned into near-stationary
segments using a modified Appel and Brandt algorithm. The modification
requires two spectral distance measures to be used to produce an
algorithm which is insensitive to changes in signal energy level which
are irrelevant in this application. Performance on real and simulated
data is presented. Segmentation has been used to provide an estimator of
the evolutive spectrum, an application to a noisy communication signal
Acoustics, Speech, and Signal Processing, 1988. ICASSP-88., 1988 International Conference on; 05/1988
[Show abstract][Hide abstract] ABSTRACT: In our previous studies, we demonstrated that infusion of apoptotic cells significantly prevented type 1 diabetes (T1D) in non-obese diabetic (NOD) mice. Extracorporeal photopheresis (ECP) is an apoptotic cell-based therapy used clinically for immune-mediated disorders. In this study, we examined the effect that intravenous delivery of apoptotic cells (ECP-treated) has in the prevention of T1D in NOD mice. We discovered that five weekly injections of ECP-treated NOD spleen cells, beginning at 8 weeks of age, significantly delayed diabetes onset. Furthermore, cell dose studies demonstrated that low dose ECP-treated spleen cells (2x10(5) cells/injection/mouse) had similar protective effects as compared to high dose (5x10(6) cells/injection). In contrast to ECP-treated cells alone, ECP-treated cells combined with beta cell antigens appeared to improve the protective effect as shown by the marked reduction in insulitis in the islets. Delivery of ECP-treated spleen cells or ECP-treated spleen cells plus beta cell antigen increased Foxp3(+) Tregs, and beta cell antigen-specific T cell proliferation was significantly suppressed in vivo in these two groups. In addition, we found that ECP-treated cells did not induce global immunosuppression or autoimmunity against nuclear antigens. In conclusion, ECP-treated cells provide a safe and effective approach in T1D prevention, suggesting that clinical ECP has great potential for managing human T1D.
[Show abstract][Hide abstract] ABSTRACT: The use of blood products to support patients undergoing the large variety of medical and surgical interventions requiring such support has continued to escalate very significantly over time. Relevantly, significant practice variation in the use of blood products exists among practitioners and institutions, largely because of the lack of robust clinical trial data, in many instances, which are critical for providing practitioners with evidence-based guidelines for appropriate blood product utilization. Recognizing this gap, the National Heart, Lung, and Blood Institute recently established a State-of-the-Science Symposium to help define areas of clinical trial research that would enhance the opportunity for developing appropriate practice guidelines for both Transfusion Medicine and Hemostasis/Thrombosis. Such a Symposium was held in September 2009 to identify important clinical trial research issues in these 2 subject areas of endeavor. The aims of this Symposium were to specifically identify phase 2 and 3 clinical trials that, if conducted over the next 5 to 10 years, could impact the treatment of patients with hemostatic and other disorders as well as to optimize the use of blood products in patients who need such interventions. This article reports on the deliberations that were held relating to the various clinical trial concepts developed by 7 Transfusion Medicine subcommittees. This Symposium generated a rich assortment of clinical trial proposals that will undergo further refinement before final implementation into pilot or full randomized clinical trials. The various proposals identified many opportunities for clinical trial research and most importantly underscored the ongoing need for well-developed evidence-based clinical trial research in the field of Transfusion Medicine.
Transfusion medicine reviews 10/2010; 24(4):259-85. DOI:10.1016/j.tmrv.2010.05.002 · 2.92 Impact Factor
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