Memory T cells in organ transplantation: progress and challenges

• Authors: Jaclyn R. Espinosa, Emory University; Kannan P. Samy, Duke University; Allan Kirk, Emory University
• Journal Title: Nature Reviews Nephrology
• Volume: Volume 12, Number 6
• Publisher: Nature Publishing Group | 2016-06, Pages 339-347
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1038/nrneph.2016.9
• Subjects: Health Sciences, Immunology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Urology & Nephrology; ALLOGRAFT SURVIVAL; HOMEOSTATIC PROLIFERATION; ANTITHYMOCYTE GLOBULIN; COSTIMULATORY BLOCKADE; ISLET TRANSPLANTATION; RENAL-TRANSPLANTATION; LYMPHOCYTE DIVISION; ADHESION MOLECULE-1; CARDIAC ALLOGRAFTS; NONHUMAN-PRIMATES; Immunologic Memory; Kidney; Organ transplantation; T cells

Abstract

Antigen-experienced T cells, also known as memory T cells, are functionally and phenotypically distinct from naive T cells. Their enhanced expression of adhesion molecules and reduced requirement for co-stimulation enables them to mount potent and rapid recall responses to subsequent antigen encounters. Memory T cells generated in response to prior antigen exposures can cross-react with other nonidentical, but similar, antigens. This heterologous cross-reactivity not only enhances protective immune responses, but also engenders de novo alloimmunity. This latter characteristic is increasingly recognized as a potential barrier to allograft acceptance that is worthy of immunotherapeutic intervention, and several approaches have been investigated. Calcineurin inhibition effectively controls memory T-cell responses to allografts, but this benefit comes at the expense of increased infectious morbidity. Lymphocyte depletion eliminates allospecific T cells but spares memory T cells to some extent, such that patients do not completely lose protective immunity. Co-stimulation blockade is associated with reduced adverse-effect profiles and improved graft function relative to calcineurin inhibition, but lacks efficacy in controlling memory T-cell responses. Targeting the adhesion molecules that are upregulated on memory T cells might offer additional means to control co-stimulation-blockade-resistant memory T-cell responses.