ORCID Profile
0000-0002-9161-7502
Current Organisations
Garvan Institute of Medical Research
,
University of Melbourne
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Publisher: Proceedings of the National Academy of Sciences
Date: 13-06-2019
Abstract: The use of specific IL-2/anti–IL-2 complexes (IL-2 cplxs) has shown great potency in the prevention of allograft rejection in mice. While long-term tolerance could be achieved toward islet allografts, clinically relevant skin graft models have remained elusive so far. Using a new protocol, this study documents that IL-2 cplxs can greatly prolong the survival of skin allografts and prevent sensitization of the recipient. The data provide support for the importance of regulatory mechanisms and organ-specific approaches when targeting allograft rejection.
Publisher: Proceedings of the National Academy of Sciences
Date: 31-12-2018
Abstract: T cells proliferate vigorously following acute depletion of CD4 + Foxp3 + T regulatory cells [natural Tregs (nTregs)] and also when naive T cells are transferred to syngeneic, nTreg-deficient Rag1 −/− hosts. Here, using mice raised in an antigen-free (AF) environment, we show that proliferation in these two situations is directed to self ligands rather than food or commensal antigens. In both situations, the absence of nTregs elevates B7 expression on host dendritic cells (DCs) and enables a small subset of naive CD4 T cells with high self affinity to respond overtly to host DCs: bidirectional T/DC interaction ensues, leading to progressive DC activation and reciprocal strong proliferation of T cells accompanied by peripheral Treg (pTreg) formation. Likewise, high-affinity CD4 T cells proliferate vigorously and form pTregs when cultured with autologous DCs in vitro in the absence of nTregs: this anti-self response is MHCII eptide dependent and elicited by the raised level of B7 on cultured DCs. The data support a model in which self tolerance is imposed via modulation of CD28 signaling and explains the pathological effects of superagonistic CD28 antibodies.
Publisher: MDPI AG
Date: 16-01-2023
DOI: 10.3390/IJMS24021752
Abstract: The clinical success of solid organ transplantation is still limited by the insufficiency of immunosuppressive regimens to control chronic rejection and late graft loss. Moreover, serious side effects caused by chronic immunosuppressive treatment increase morbidity and mortality in transplant patients. Regulatory T cells (Tregs) have proven to be efficient in the induction of allograft tolerance and prolongation of graft survival in numerous preclinical models, and treatment has now moved to the clinics. The results of the first Treg-based clinical trials seem promising, proving the feasibility and safety of Treg therapy in clinical organ transplantation. However, many questions regarding Treg phenotype, optimum dosage, antigen-specificity, adjunct immunosuppressants and efficacy remain open. This review summarizes the results of the first Treg-based clinical trials for tolerance induction in solid organ transplantation and recapitulates what we have learnt so far and which questions need to be resolved before Treg therapy can become part of daily clinical practice. In addition, we discuss new strategies being developed for induction of donor-specific tolerance in solid organ transplantation with the clinical aims of prolonged graft survival and minimization of immunosuppression.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 03-05-2019
Abstract: Food antigens drive spontaneous IgE elevation in the absence of microbiota by inducing IL-4–producing T follicular helper cells.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 15-06-2021
DOI: 10.1126/SCIIMMUNOL.ABJ9256
Abstract: The side effects of SARS-CoV-2 vaccines are often troubling but may merely reflect transient production of type I interferons, a normal physiological response to contact with invading microorganisms.
No related grants have been discovered for Jonathan Sprent.