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

• Published in: Bone marrow transplantation (Basingstoke) Vol. 46; no. 11; pp. 1437 - 1443
• Main Authors: Tormo, N, Solano, C, Benet, I, Nieto, J, de la Camara, R, Lopez, J, Garcia-Noblejas, A, Munoz-Cobo, B, Costa, E, Clari, M A, Hernandez-Boluda, J C, Remigia, M J, Navarro, D
• Format: Journal Article
• Language: English
• Published: 01.11.2011
• Subjects: Bone marrow transplantation; CD4 antigen; CD8 antigen; Cytomegalovirus; Donors; gamma -Interferon; Globulins; Hemopoiesis; Histocompatibility antigen HLA; Lymphocytes T; pp65 protein; Thymocytes; Umbilical cord
• ISSN: 0268-3369
• DOI: 10.1038/bmt.2010.330

Threshold levels of CMV-specific T-cell populations presumably affording protection from active CMV infection in allo-SCT recipients have been proposed, but lack extensive validation. We quantified CMV pp65 and immediate-early 1-specific IFN- gamma CD8 super(+) and CD4 super(+) T cell responses at days +30, +60 and +90 after transplantation in 133 patients, and established cutoff cell levels protecting from CMV DNAemia within the first 120 days after transplantation. No patients showing IFN- gamma CD8 super(+) or IFN- gamma CD4 super(+) T-cell counts >1.0 and >1.2 cells/ mu L, respectively, developed a subsequent episode of CMV DNAemia. Initial or recurrent episodes of CMV DNAemia occurred in the face of IFN- gamma T-cell levels below defined thresholds. Negative predictive values at day +30 for the IFN- gamma CD8 super(+) and CD4 super(+) T-cell markers were 68.1 and 61.8%, respectively. Recipients of grafts from CMV seropositive, related or HLA-matched donors, or receiving non-myeloablative conditioning had nonsignificant tendencies to reach more frequently protective levels of both T-cell subsets at early and late (day +365) times after transplantation. The use of anti-thymocyte globulin and umbilical cord blood transplantation were associated with impaired CMV-specific T-cell reconstitution. CMV-specific IFN- gamma CD8 super(+) and CD4 super(+) T-cell recovery occurred irrespective of detectable CMV DNAemia.