RESUMEN
The effect of programmed death 1 (PD-1) on cytomegalovirus (CMV)-specific T cells has not been thoroughly examined. We evaluated the involvement of exhausted CMV-specific T cells in persistent CMV infection after allogeneic hematopoietic stem cell transplantation (HSCT). CMV-specific CD8+ T cells obtained from an HLA-A∗24:02-positive patient, who failed to eliminate CMV for more than 1 year after HSCT, responded poorly to CMV pp65 peptide and showed high PD-1 expression. Sera from patients with persistent CMV infection showed a significantly higher IL-6 level than those from patients with temporary CMV infection after allogeneic HSCT and healthy donors. CD33+ adherent cells produced IL-6, and regulated PD-1 expression and growth of CMV-specific CD8+ T cells through cell-to-cell contact. Although further investigation is required to clarify the association between IL-6 level and CMV infection in more patients, IL-6 might be a useful biomarker of persistent CMV infection after allogeneic HSCT.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Infecciones por Citomegalovirus/genética , Citomegalovirus/inmunología , Trasplante de Células Madre Hematopoyéticas , Interleucina-6/genética , Receptor de Muerte Celular Programada 1/genética , Linfocitos T CD8-positivos/patología , Adhesión Celular , Comunicación Celular , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/patología , Infecciones por Citomegalovirus/virología , Expresión Génica , Antígeno HLA-A24/genética , Antígeno HLA-A24/inmunología , Interacciones Huésped-Patógeno , Humanos , Tolerancia Inmunológica , Interleucina-6/inmunología , Masculino , Persona de Mediana Edad , Receptor de Muerte Celular Programada 1/inmunología , Lectina 3 Similar a Ig de Unión al Ácido Siálico/genética , Lectina 3 Similar a Ig de Unión al Ácido Siálico/inmunología , Transducción de Señal , Trasplante Homólogo , Carga ViralRESUMEN
A case of leukemia escape from an HLA-specific cytotoxic T lymphocyte (CTL) response in a recipient of bone marrow transplantation is presented. Only the expression of HLA-B51, which was a mismatched HLA locus in the graft-versus-host direction, was down-regulated in post-transplant leukemia blasts compared with that in pre-transplant blasts. All CTL clones, that were isolated from the recipient's blood when acute graft-versus-host disease developed, recognized the mismatched B(∗)51:01 molecule in a peptide-dependent manner. The pre-transplant leukemia blasts were lysed by CTL clones, whereas the post-transplant leukemia blasts were not lysed by any CTL clones. The IFN-γ ELISPOT assay revealed that B(∗)51:01-reactive T lymphocytes accounted for the majority of the total alloreactive T lymphocytes in the blood just before leukemia relapse. These data suggest that immune escape of leukemia blasts from CTL pressure toward a certain HLA molecule can lead to clinical relapse after bone marrow transplantation.