Reconstitution of cytomegalovirus‐specific T‐cell response in allogeneic hematopoietic stem cell recipients: the contribution of six frequently recognized, virus‐encoded ORFs

Abstract

The individual peptide pools and native HCMV antigens were useful for monitoring the time course of the anti-HCMV response by IFNγ-ELISPOT, which proved to have a prognostic value. Besides widely employed peptide pools of pp65 and IE-1, the use of antigens UL36 and UL55, but not US3 or US29, increased sensitivity of the test.

Rapid reconstitution of CMV‐specific T‐cells after stem‐cell transplantation

“…These individuals showed a delayed reconstitution of CMV‐specific CD4 T‐cells, supporting the concept of a predominant role of cellular immunity to prevent CMV‐viremia. This is also in line with results from other studies showing that low CMV‐specific T‐cell levels correlate with active infection, or are associated with a higher incidence of viremia in the 30 days following sampling . The delay in CMV‐specific immune reconstitution preferentially occurs in seropositive recipients of a seronegative donor, where de novo priming of CMV‐specific T‐cells is required, unless residual recipient‐derived memory T‐cells are expanding.…”

“…This is also in line with results from other studies showing that low CMV-specific T-cell levels correlate with active infection, 13,14,27,28 or are associated with a higher incidence of viremia in the 30 days following sampling. 35 The delay in CMVspecific immune reconstitution preferentially occurs in seropositive recipients of a seronegative donor, where de novo priming of CMV-specific T-cells is required, unless residual recipient-derived memory T-cells are expanding. Furthermore, the delay may result from the fact that CMV-specific T-cells may be functionally impaired in the presence of active replication.…”

Patient risk stratification and tailored clinical management of post‐transplant CMV‐, EBV‐, and BKV‐infections by monitoring virus‐specific T‐cell immunity

“…Although the correlation between VST presence and viral control has been demonstrated post‐solid organ transplantation for all three viruses [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ], reports in the HCT setting mostly have focused on CMV [ 16 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. In our study, by simultaneously monitoring functional T‐cell immunity against a broad spectrum of clinically problematic viruses after allo‐HCT, in conjunction with viral load, we showed that VST rebounds, even in patients with viral diseases, were associated with marked reductions of the relevant viral loads and a favorable clinical outcome.…”

Viral Infections in HSCT: Detection, Monitoring, Clinical Management, and Immunologic Implications

“…Combining HLA-multimer-bound CMV-peptides and CMV-peptide-induced cytokines, notably gamma-interferon, has been proposed as a suitable method for recognizing CMV specific T-cell; peptides deriving from the CMV p65 and immediate-early 1 (IE-1) proteins have been regarded as the best promising viral markers to be detected ( 23 ). Other CMV proteins, as pUL97, have been more recently proposed as possible alternative or complementary diagnostic tools ( 24 ), while HLA multimers and cytokine release represent the favorite methods to retrieve virus-specific T-lymphocytes for adoptive therapy. A limitation of HLA-multimers is that they are HLA-restricted and recognized only by CD8 cells, being almost exclusively class I.…”