The immunosuppressive effect of human cytomegalovirus infection in recipients of allogeneic hematopoietic stem cell transplantation

Abstract

Summary:In immune-competent individuals, human cytomegalovirus (HCMV) infection is associated with impairment of T-cell function. Our goal was to evaluate prospectively whether clinically asymptomatic HCMV infection in allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients, treated pre emptively with ganciclovir, influences T-cell function as well. Mitogen-stimulated T-cell proliferative activity, together with cell surface markers, was tested in 49 patients on days þ 30, þ 45, þ 60, and þ 90 after alloHSCT and, additionally, in cases of positive HCMV pp65-antigenemia. HCMV infection was diagnosed in 19 patients. None of them developed HCMV disease. T-cell proliferative activity was significantly decreased on days when HCMV antigenemia was positive as compared to days without antigenemia. The number of pp65-positive cells negatively correlated with proliferative response. Comparison of patients who did experience HCMV infection with those who did not reveals significant decrease of T-cell proliferative activity observed on days þ 30 and þ 45, a time period when antigenemia was most frequently found to be positive, whereas no difference was detected on days þ 60 and þ 90. We conclude that, even clinically asymptomatic, HCMV infection has negative impact on T-cell proliferation capacity in alloHSCT recipients. However, pre emptive therapy with ganciclovir makes this immunosuppressive effect transient and restricted to the time of infection duration.

T-cell receptor αβ+ and CD19+ cell–depleted haploidentical and mismatched hematopoietic stem cell transplantation in primary immune deficiency

“…All grafts were TCRab 1 /CD19 1 depleted by using an immunomagnetic method, according to the manufacturer's recommendations (Miltenyi Biotec, Bergisch Gladbach, Germany). Most patients (80.7%) received reduced-toxicity myeloablative conditioning consisting of treosulfan (36)(37)(38)(39)(40)(41)(42) (Table I). Cyclosporine (trough target 50-100 mmol/L) and mycophenolate mofetil were used for 12 and 6 weeks after HSCT, respectively, unless required longer for GvHD.…”

The Human Cytomegalovirus UL11 Protein Interacts with the Receptor Tyrosine Phosphatase CD45, Resulting in Functional Paralysis of T Cells

“…Acute CMV infection results in a reduction in the proliferation capacity of lymphocytes, which are not themselves infected by the virus [11]. A similar effect is produced in vitro upon contact between lymphocytes and CMV-infected cells, indicating the potential existence of uncharacterized surface expressed viral proteins with immunomodulatory properties [12], [21].…”

The human cytomegalovirus glycoprotein pUL11 acts via CD45 to induce T cell IL-10 secretion

“…Infected cells are masked from recognition and have their functions manipulated to the benefit of the virus. Uninfected immune cells are also affected; a generalized myelosuppression has been described, the ability of peripheral blood mononuclear cells (PBMC) to proliferate in response to stimuli is reduced and the cytokine profile is altered [5,7–9]. The mechanisms by which uninfected cells are manipulated are not yet fully understood but appear to involve both direct contact with infected cells and also the actions of secreted factors [10,11].…”