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Human Monoclonal Antibodies and Immune Modulation in Viral Hepatitis, Schistosomiasis, and HTLV Infection
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Thomas F. Kresina, Garry A. Neil, Steven K. H. Foung
For acute hepatitis B virus infection, approximately 90% of infections of adults resolve with the development of protective antibodies [49]. Individuals vaccinated with viral surface antigen generate a substantial antiviral antibody response. On the basis of these observations, the concept of adoptive transfer of protective antibody-based immunity has been proposed [50], Adoptive transfer of protective immunity may represent a viable approach for application to immunologically non-responsive individuals, such as liver transplantation recipients. Integral to this approach is the characterization of the protective antibody response and eplication as human monoclonal antibodies.
Immunogenetics and Immunopathogenesis of the NOD Mouse
Published in George S. Eisenbarth, Immunotherapy of Diabetes and Selected Autoimmune Diseases, 2019
Hiroshi Ikegami, Nabuki Yano, Toshiaki Sato, Masakazu Hattori
Studies utilizing adoptive transfer system showed controversial results regarding T cell subsets involved in the disease transfer. Transfer experiments by Miller and co-workers34 utilizing irradiated young NOD mice as recipients suggested that both L3T4 + and Lyt2 + T cells are necessary for the disease transfer. Neither L3T4 + cells nor Lyt2 + cells alone were able to transfer the disease, but when the two subsets were cotransferred, most recipients developed diabetes. In addition, their data indicated that both subsets must be obtained from diabetic donors. Neither subset can be replaced with cells from young, nondiabetic donors. These data suggest that donor cells must be activated or primed like cells in diabetic animals to transfer the disease.
Role of Cell-Mediated Immunity in Resistance to Malaria
Published in Mary M. Stevenson, Malaria: Host Responses to Infection, 2017
Johanne Melancon-Kaplan, William P. Weidanz
In addition, antibody-independent resistance to assorted hemoprotozoa has been achieved by the injection of various immunomodulating agents.19 The most compelling evidence that nonantibody T cell-dependent immune mechanisms can mediate resistance to malaria has been obtained from studies utilizing B cell-deficient hosts which resolved acute infections 9with blood-stage parasites spontaneously27 or resisted reinfection following chemotherapy.28–30 The finding of Chen et al.31 that B cell-deficient mice immunized with irradiated P. berghei sporozoites were resistant to challenge with viable sporozoites demonstrated that resistance to this stage of the parasite could be mediated by T cell-dependent immune mechanisms as well. The results of adoptive transfer studies employing immune T cells, antigen-specific T cell lines, and T cell clones provide definitive evidence in support of this concept (see below).
Tumor-infiltrating lymphocytes for adoptive cell therapy: recent advances, challenges, and future directions
Published in Expert Opinion on Biological Therapy, 2022
Joachim Stoltenborg Granhøj, Agnete Witness Præst Jensen, Mario Presti, Özcan Met, Inge Marie Svane, Marco Donia
Current TIL production protocols use HD IL-2 to sustain and promote the rapid expansion of TILs. However, IL-2 promotes the generation of terminally differentiated TILs reliant on glycolytic metabolism [131,159]. As presented above, several factors present within the TME could potentially limit the ability of TILs to engage in anaerobic glycolysis. As a result, TILs could face severe metabolic stress upon adoptive transfer as the metabolic demand needed to sustain their antitumor effector functions cannot be fulfilled [131]. Ultimately, this could reduce TIL persistence and antitumor efficacy upon adoptive transfer [124,159]. Understanding the metabolic pathways necessary for optimal TIL effector functionality and longevity could provide essential information needed to optimize the TIL expansion protocol and improve the clinical outcome in TIL-based ACT in the future.
Safety considerations with current and emerging antiviral therapies for cytomegalovirus infection in transplantation
Published in Expert Opinion on Drug Safety, 2019
Guy El Helou, Raymund R Razonable
Knowledge of the potential interaction of anti-CMV drugs with other medications used in the complex transplant population is highly encouraged, as there may be potential additive and synergistic adverse outcomes. All of these safety variables will need to be considered, in addition to their efficacy profiles (not discussed in detail here), in choosing the best antiviral drug for the prevention and treatment of HCMV in the transplant setting. Finally, the authors recommend that the management of HCMV infection after transplantation should always take into account the fact that this virus became opportunistic as a result of severe impairment in immune function. Thus, we encourage discussing reduction in immunosuppressive drug doses with the multidisciplinary transplant teams. The use of IVIG or CMV IG, or the adoptive transfer of HCMV-specific T cells, may also be considered in selected cases. Among these immunomodulatory strategies, reduction in immunosuppression is an accepted practice, albeit not standardized, while the use of IVIG and CMV IG remains hotly debated. In contrast, adoptive transfer of HCMV-specific T cells remains investigational, and even though promising data exist in regards to its efficacy, its safety profile needs to be better defined. As novel and investigational antiviral drugs and strategies are being developed, their role for HCMV management will depend not only on demonstrated efficacy but also on safety considerations that will play an equally important role.
Topical Quercetin and Resveratrol Protect the Ocular Surface in Experimental Dry Eye Disease
Published in Ocular Immunology and Inflammation, 2019
Antonio Abengózar-Vela, Chris S. Schaumburg, Michael E. Stern, Margarita Calonge, Amalia Enríquez-de-Salamanca, María Jesús González-García
The adoptive transfer model was performed as previously described.27,31 CD4+ T cells from each group of DS-exposed mice were isolated from spleens and cervical lymph nodes, and enriched using a CD4+ T cell isolation kit II (MACS System, Miltenyi Biotec, Auburn, CA, USA), according to the manufacturer’s instructions. Then, one donor-equivalent [defined as the number CD4+ T cells remaining after the respective in-vitro manipulation of a single set of lymph nodes or spleen (approximately 5 × 106 CD4+ T cells)] of cell suspension in phosphate-buffered saline (PBS) was transferred intraperitoneally into each T-cell-deficient athymic nude C57BL/6 mouse (recipient mouse). Eight recipient mice per donor group were used. Recipient mice were sacrificed 72 h after receiving adoptively transferred CD4+ T cells. Immediately, left eyeballs with attached lids were embedded in optimal cutting temperature (OCT) compound and flash frozen until use.