Application of Mass Cytometry Platforms to Solid Organ Transplantation.

Transplantation serves as the cornerstone of treatment for patients with end-stage organ disease. The prevalence of complications, such as allograft rejection, infection, and malignancies, underscores the need to dissect the complex interactions of the immune system at the single-cell level. In this review, we discuss studies using mass cytometry or cytometry by time-of-flight, a cutting-edge technology enabling the characterization of immune populations and cell-to-cell interactions in granular detail. We review the application of mass cytometry in human and experimental animal studies in the context of transplantation, uncovering invaluable contributions of the tool to understanding rejection and other transplant-related complications. We discuss recent innovations that have the potential to streamline and standardize mass cytometry workflows for application to multisite clinical trials. Additionally, we introduce imaging mass cytometry, a technique that couples the power of mass cytometry with spatial context, thereby mapping cellular interactions within tissue microenvironments. The synergistic integration of mass cytometry and imaging mass cytometry data with other omics data sets and high-dimensional data platforms to further define immune dynamics is discussed. In conclusion, mass cytometry technologies, when integrated with other tools and data, shed light on the intricate landscape of the immune response in transplantation. This approach holds significant potential for enhancing patient outcomes by advancing our understanding and facilitating the development of new diagnostics and therapeutics.

Epstein-Barr virus peptides derived from latent cycle proteins alter NKG2A + NK cell effector function.

Natural killer (NK) cells control viral infection through the interaction between inhibitory receptors and human leukocyte antigen (HLA) ligands and bound peptide. NK cells expressing the inhibitory receptor NKG2A/CD94 recognize and respond to autologous B cells latently infected with Epstein-Barr virus (EBV). The mechanism is not yet understood, thus we investigated peptides derived from seven latent proteins of EBV in the interaction of NKG2A and its ligand HLA-E. Functional analysis demonstrated that EBV peptides can bind to HLA-E and block inhibition of NK cell effector function. Moreover, analysis of DNA from 79 subjects showed sequence variations in the latent protein, LMP1, which alters NK responses to EBV. We provide evidence that peptides derived from EBV latent cycle proteins can impair the recognition of NKG2A despite being presented by HLA-E, resulting in NK cell activation.

Natural killer cells as modulators of alloimmune responses.

PURPOSE OF REVIEW: Natural killer (NK) cells are effector cells of the innate immune system that can lyse target cells without prior sensitization and are important in host defense to virally infected and transformed cells. Although the concept of 'missing-self' would suggest NK cells could target foreign allografts, the prevailing dogma has been that NK cells are not active participants in the rejection of solid organ allografts. This review summarizes recent studies that challenge this conclusion and instead suggest NK cells are important in outcomes posttransplant. RECENT FINDINGS: NK cells expressing specific cell surface receptors may promote graft damage and rejection. However, recent studies suggest some NK cell subsets have tolerogenic or immunoregulatory potential and promote graft stability, suggesting a dichotomous role for NK cells after transplant. Furthermore, NK cells respond to cells infected with cytomegalovirus and Epstein-Barr virus, and studies suggest some NK cells have immune memory. SUMMARY: Our understanding of the role of NK cells posttransplant has evolved from 'no role' to the current idea that NK cells may have 'complex interactions' that impact graft outcomes. Additional studies, using cutting edge techniques to comprehensively analyze the phenotypic and functional subsets of NK cells in transplant recipients, are clearly necessary.