Relationship of Reconstituted Adaptive and Innate Cytomegalovirus (CMV)–Specific Immune Responses with CMV Viremia in Hematopoietic Stem Cell Transplant Recipients

Abstract

To our knowledge, this is the first study to prospectively compare multiple measures of innate and adaptive immune responses in hematopoietic stem cell transplant recipients with CMV viremia. The strongest immune correlates with protection against CMV viremia in hematopoietic stem cell transplant recipients are reconstitution of CMV-specific T cell memory responses (LPA) and recovery of natural killer cell function. In contrast, positive CMV-LPA before transplantation may be a marker of high risk of CMV reactivation after transplantation.

Reconstitution of CMV pp65 and IE-1-specific IFN-γ CD8+ and CD4+ T-cell responses affording protection from CMV DNAemia following allogeneic hematopoietic SCT

“…13,[21][22][23][24][25] In addition, T-cell responses against viral proteins other than pp65 and IE-1, or other functional anti-CMV immune responses such as those mediated by NK cells, which may critically contribute to the control of CMV infection, were not examined in this study. 26,27 Clearly, the IFN-g CD4 þ T-cell marker performed worse than the IFN-g CD8 þ T-cell marker in predicting the risk of CMV DNAemia. In this sense, it has to be taken into consideration that our analytical method is less suited for assessing CMV-specific CD4 þ than CD8 þ T-cell responses (use of overlapping peptide libraries and pp65 and IE-1 as stimulating Ags).…”

Cytomegalovirus shapes long-term immune reconstitution after allogeneic stem cell transplantation

“…[11][12][13] However, complex and heterogeneous clinical settings such as cGvHD often simultaneously affect several immune cell populations. 3 While molecular biology 8 and functional assays 14 can be used to study immune reconstitution, flow cytometry uniquely allows the simultaneous assessment of several immune populations. 9 Multivariate methods such as clustering algorithms, and principal component analyses are widely used to analyze multidimensional data such as gene expression profiles, but these methods have also been successfully applied to other types of data, such as clinical symptoms and murine hematopoietic reconstitution.…”

Favorable impact of natural killer cell reconstitution on chronic graft-versus-host disease and cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation

“…[39][40][41] In addition, recovery of NK cell function has been correlated with protection against CMV. 42 Although the studies providing this information were conducted on relatively small cohorts, the results indicate that the reconstitution of NK cells after allogeneic HSCT may be decisive in the early control of CMV reactivation. NK cells from mice challenged with murine CMV undergo all four phases of an immune response against a pathogen: clonal-like expansion, involving the Ly49H + NK cell subset, contraction and then a memory-like phase, with heightened responses to re-challenge by the same antigen.…”