Recollective homeostasis and the immune consequences of peritransplant depletional induction therapy

• Type of Material: Article
• Authors: Joshua M Rosenblum, Emory University; Allan Kirk, Emory University
• Language: English
• Date: 2014-03-01
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 John Wiley & Sons A/S.
• Final Published Version (URL): http://dx.doi.org/10.1111/imr.12155
• Title of Journal or Parent Work: Immunological Reviews
• ISSN: 0105-2896
• Volume: 258
• Issue: 1
• Start Page: 167
• End Page: 182
• Keywords: VERSUS-HOST-DISEASE; T-CELL DEPLETION; tolerance; KIDNEY-TRANSPLANT RECIPIENTS; BONE-MARROW-TRANSPLANTATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; OKT3 MONOCLONAL-ANTIBODY; Immunology; Science & Technology; induction; memory T cell; transplantation; Life Sciences & Biomedicine; homeostasis; RABBIT ANTITHYMOCYTE GLOBULIN; DOSE CYCLOSPORINE MONOTHERAPY; DONOR-SPECIFIC TRANSFUSION; CARDIAC ALLOGRAFT SURVIVAL
• Research Categories: Health Sciences, Immunology; Health Sciences, Medicine and Surgery

Abstract

One's cellular immune repertoire is composed of lymphocytes in multiple stages of maturation - the dynamic product of their responses to antigenic challenges and the homeostatic contractions necessary to accommodate immune expansions within physiologic norms. Given that alloreactivity is predominantly a cross-reactive phenomenon that is stochastically distributed throughout the overall T-cell repertoire, one's allospecific repertoire is similarly made up of cells in a variety of differentiation states. As such, the continuous expansion and elimination of activated memory populations, producing a 'recollective homeostasis' of sorts, has the potential over time to alter the maturation state and effector composition of both ones protective and alloreactive T-cell repertoire. Importantly, a T cell's maturation state significantly influences its response to numerous immunomodulatory therapies used in organ transplantation, including depletional antibody induction. In this review, we discuss clinically utilized depletional induction strategies, how their use alters a transplant recipient's cellular immune repertoire, and how a recipient's repertoire influences the clinical effects of induction therapy.