Late-onset cytomegalovirus (CMV) in lung transplant recipients: can CMV serostatus guide the duration of prophylaxis?

Evidence supports the use of 12 months of cytomegalovirus prophylaxis in all at-risk lung transplants; whether cytomegalovirus serostatus can be used to further optimize this duration remains to be determined. The purpose of this retrospective study was to determine if cytomegalovirus serostatus of both donor and recipient were associated with late-onset cytomegalovirus. The primary outcome was the proportion of lung transplants that developed cytomegalovirus infection or disease during the 180-day period following 6 months of prophylaxis in each at-risk serotype. Two hundred forty-four consecutive lung transplants were evaluated, 131 were included. The proportion of recipients with cytomegalovirus differed significantly between serotypes (20 of 41 [48.8%] D+/R- vs. 19 of 56 [33.9%] D+/R+ vs. 2 of 34 [5.9%] D-/R+; p < 0.001). In a multivariate model, older age (odds ratio [OR], 1.05, 95% confidence interval [CI] 1.004-1.099; p = 0.03) and D+/R- serostatus (OR, 3.83; 95% CI 1.674-8.770; p = 0.002) were associated with cytomegalovirus. Among R+ lung transplants, D- serostatus was associated with the absence of cytomegalovirus (OR, 0.12; 95% CI 0.0263-0.563; p = 0.007). These findings suggest that in the valganciclovir era, cytomegalovirus serostatus of both donor and recipient may identify lung transplants at heightened risk for late-onset cytomegalovirus.

Prolongation of cardiac allograft survival by a novel population of autologous CD117+ bone marrow-derived progenitor cells.

Autologous CD117(+) progenitor cells (PC) have been successfully utilized in myocardial infarction and ischemic injury, potentially through the replacement/repair of damaged vascular endothelium. To date, such cells have not been used to enhance solid organ transplant outcome. In this study, we determined whether autologous bone marrow-derived CD117(+) PC could benefit cardiac allograft survival, possibly by replacing donor vascular cells. Autologous, positively selected CD117(+) PC were administered posttransplantation and allografts were assessed for acute rejection. Although significant generation of recipient vascular cell chimerism was not observed, transferred PC disseminated both to the allograft and to peripheral lymphoid tissues and facilitated a significant, dose-dependent prolongation of allograft survival. While CD117(+) PC dramatically inhibited alloreactive T cell proliferation in vitro, this property did not differ from nonprotective CD117(-) bone marrow populations. In vivo, CD117(+) PC did not significantly inhibit T cell alloreactivity or increase peripheral regulatory T cell numbers. Thus, rather than inhibiting adaptive immunity to the allograft, CD117(+) PC may play a cytoprotective role in prolonging graft survival. Importantly, autologous CD117(+) PC appear to be distinct from bone marrow-derived mesenchymal stem cells (MSC) previously used to prolong allograft survival. As such, autologous CD117(+) PC represent a novel cellular therapy for promoting allograft survival.

The tetraspanin CD9 influences the adhesion, spreading, and pericellular fibronectin matrix assembly of Chinese hamster ovary cells on human plasma fibronectin.

The role of CD9 in cell adhesion and spreading on adhesive proteins was investigated using a transfected Chinese hamster ovary (CHO) cell system. CD9 cell surface expression resulted in reduced adhesion and increased spreading on fibronectin (Fn). Whereas mock-transfected (mock CHO) and naïve CHO cells assumed a typical fibroblast spindle shape morphology, CD9-transfected (CD9-CHO) cells were polygonal with many filipodial projections and exhibited a twofold greater surface area. The spread morphology of CD9-CHO cells, but not mock CHO cells, was inhibited by PB1 mAb blockade of alpha(5)beta(1), suggesting that the coexpression of alpha(5)beta(1) and CD9 influenced cell activity on Fn. The second extracellular loop of CD9 was implicated in regulation of adhesion since reduced CD9-CHO cell adhesion on Fn was reversed by either anti-CD9 antibody ligation to the second extracellular loop or with cells expressing a CD9 mutant lacking the second extracellular loop domain. Using cell adhesion assays and ELISA, we demonstrated CD9 binding to the HEP2/IIICS region of Fn. Finally, CD9 expression resulted in a twofold reduction in Fn-rich pericellular matrix assembly. Our observations show that CD9 dramatically influences CHO cell interactions with Fn and suggest that CD9 has an important role in modulating cell-extracellular matrix interactions.