Monitoring cytomegalovirus IE-1 and pp65-specific CD4+ and CD8+ T-cell responses after allogeneic stem cell transplantation may identify patients at risk for recurrent CMV reactivations.

We studied the recovery of CMV-specific CD4+ and CD8+ T-cell immunity in 52 recipients of allogeneic stem cell transplantation (SCT). The proportions of IFN-gamma-producing CD4+ and CD8+ T cells upon in vitro activation using peptide pools representing the CMV pp65 and IE-1 proteins were assessed at multiple time points post SCT, and correlated with the occurrence of CMV reactivation. In a retrospective analysis, recurrent CMV reactivations occurred in 9 patients and were associated with low pp65-specific CD4+ T-cell and low IE-1-specific CD8(+) T-cell reactivities, whereas patients without detectable CMV reactivation (n = 30) or a single reactivation (n = 13) showed a better recovery of these immune responses. CD4+ T-cell responses to IE-1 were infrequent in most patients, whereas CD8+ T-cell responses to pp65 occurred frequently, but did not correlate with protection against (recurrent) reactivation. Prospectively, CMV-specific T-cell responses could be studied prior to 14 reactivation episodes in 8 patients. CD4+ T-cell responses to IE-1 and pp65 were positive in only 1 and 2 episodes, respectively. CD8+ T-cell responses against IE-1 were positive in 4, but against pp65 in 12 episodes, again showing that CD8+ T-cell reactivity against pp65 did not prevent CMV reactivation. Thus, monitoring of particular CMV-specific CD4+ and CD8+ T-cell responses after allogeneic SCT may identify patients at risk for recurrent CMV reactivations.

Gratama JW ，Brooimans RA ，van der Holt B ，Sintnicolaas K ，van Doornum G ，Niesters HG ，Löwenberg B ，Cornelissen JJ ... -  《-》

High levels of CMV-IE-1-specific memory T cells are associated with less alloimmunity and improved renal allograft function.

Nickel P ，Bold G ，Presber F ，Biti D ，Babel N ，Kreutzer S ，Pratschke J ，Schönemann C ，Kern F ，Volk HD ，Reinke P ... -  《TRANSPLANT IMMUNOLOGY》

Kinetics of cytomegalovirus (CMV) pp65 and IE-1-specific IFNgamma CD8+ and CD4+ T cells during episodes of viral DNAemia in allogeneic stem cell transplant recipients: potential implications for the management of active CMV infection.

The dynamics of CMV pp65 and IE-1-specific IFNgamma-producing CD8(+) (IFNgamma CD8(+)) and CD4(+) (IFNgamma CD4(+)) T cells and CMV DNAemia were assessed in 19 pre-emptively treated episodes of active CMV infection. Peripheral counts of IFNgamma CD8(+) and IFNgamma CD4(+) T cells inversely correlated with CMV DNAemia levels (P = <0.001 and P = 0.003, respectively). A threshold value of 1.3 cells/microl predicting CMV DNAemia clearance was established for IFNgamma CD8(+) T cells (PPV, 100%; NPV, 93%) and for IFNgamma CD4(+) T cells (PPV, 100%; NPV, 75%). Undetectable T-cell responses were usually observed at the time of initiation of pre-emptive therapy. Either a rapid (within 7 days) or a delayed (median 31 days) expansion of both T-cell populations concomitant with CMV DNAemia clearance was observed in 5 and 8 episodes, respectively. An inconsistent or a lack of expansion of both T-cell subsets was related to a persistent CMV DNAemia. Robust and maintained CMV-specific T-cell responses after CMV DNAemia clearance and cessation of antiviral therapy were associated with a null incidence of relapsing infections at least during the following month. Data obtained in the present study may be helpful in the design of therapeutic strategies for the management of active CMV infections in the allo-SCT recipient.

Tormo N ，Solano C ，Benet I ，Nieto J ，de la Cámara R ，Garcia-Noblejas A ，Clari MA ，Chilet M ，López J ，Hernández-Boluda JC ，Remigia MJ ，Navarro D ... -  《-》

Cytomegalovirus immune reconstitution occurs in recipients of allogeneic hematopoietic cell transplants irrespective of detectable cytomegalovirus infection.

Gallez-Hawkins G ，Thao L ，Lacey SF ，Martinez J ，Li X ，Franck AE ，Lomeli NA ，Longmate J ，Diamond DJ ，Spielberger R ，Forman SJ ，Zaia JA ... -  《BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION》

Lack of prompt expansion of cytomegalovirus pp65 and IE-1-specific IFNgamma CD8+ and CD4+ T cells is associated with rising levels of pp65 antigenemia and DNAemia during pre-emptive therapy in allogeneic hematopoietic stem cell transplant recipients.

Tormo N ，Solano C ，Benet I ，Clari MA ，Nieto J ，de la Cámara R ，López J ，López-Aldeguer N ，Hernández-Boluda JC ，Remigia MJ ，Garcia-Noblejas A ，Gimeno C ，Navarro D ... -  《-》