Impact of cytomegalovirus and grafts versus host disease on the dynamics of CD57+CD28-CD8+ T cells after bone marrow transplant

OBJECTIVES: The present study aimed to evaluate the dynamics of CD28 and CD57 expression in CD8+ T lymphocytes during cytomegalovirus viremia in bone marrow transplant recipients. METHODS: In a prospective study, blood samples were obtained once weekly once from 33 healthy volunteers and weekly from 33 patients. To evaluate the expression of CD57 and CD28 on CD8+ T lymphocytes, flow cytometry analysis was performed on blood samples for four months after bone marrow transplant, together with cytomegalovirus antigenemia assays. RESULTS: Compared to cytomegalovirus-seronegative healthy subjects, seropositive healthy subjects demonstrated a higher percentage of CD57+ and a lower percentage of CD28+ cells (p<0.05). A linear regression model demonstrated a continuous decrease in CD28+ expression and a continuous increase in CD57+ expression after bone marrow transplant. The occurrence of cytomegalovirus antigenemia was associated with a steep drop in the percentage of CD28+ cells (5.94 percent, p<0.01) and an increase in CD57+ lymphocytes (5.60 percent, p<0.01). This cytomegalovirus-dependent effect was for the most part concentrated in the allogeneic bone marrow transplant patients. The development of acute graft versus host disease, which occurred at an earlier time than antigenemia (day 26 vs. day 56 post- bone marrow transplant), also had an impact on the CD57+ subset, triggering an increase of 4.9 percent in CD57+ lymphocytes (p<0.05). CONCLUSION: We found continuous relative changes in the CD28+ and CD57+ subsets during the first 120 days post- bone marrow transplant, as part of immune system reconstitution and maturation. A clear correlation was observed between the expansion of the CD57+CD28-CD8+ T lymphocyte subpopulation and the occurrence of graft versus host disease and cytomegalovirus viremia.

Chimeric dengue type 2/type 1 viruses induce immune responses in cynomolgus monkeys.

Chimeric dengue type 2/type 1 (DEN2/1) viruses, which contain the structural genes of the dengue-1 (16007) parental virus and the nonstructural genes of the DEN2-PDK53 virus, have been constructed. These DEN2/1 viruses induce high levels of DEN1 virus-specific neutralizing antibodies in mice. In this study, the DEN2/1 viruses induced DEN1 virus-specific neutralizing antibodies without the development of viremia in cynomolgus monkeys. Dengue virus-specific IgM antibodies were detected in the sera of the immunized animals as early as 3 days post-immunization. After challenge with the DEN1-16007 wild-type virus, only a low level of viremia was detected in chimeric DEN2/1 virus-immunized monkeys. A second challenge, with DEN2-16681 virus, was given while the levels of DEN2-specific neutralizing antibodies were very low: infectious Dengue 2 virus could not be detected in sera of the monkeys. A correlation between the level of neutralizing antibody and the incidence of viremia could not be found. In addition, there was no significant increase in the levels of interferon gamma and soluble interleukin 2 receptor in the sera of the challenged monkeys, which suggests a reduction in immunopathogenesis caused by T-cell activation. Our findings suggest that DEN2/1 viruses may used as a live-attenuated candidate vaccine because of their safety, broad immunogenicity, and lower immunopathogenicity.