Cellular immune parameters associated with spontaneous control of CMV in children who underwent transplantation

Abstract

CD4 þ T-cell functions that best correlate with CMV control were evaluated by studying the relationship between CMV infection and CMV-specific immune recovery as determined by proliferation assay and intracytoplasmic-IFNc assay. A total of 30 children (mean age: 8.30 years) who received an allogeneic hematopoietic SCT (HSCT) were included. In total, 13 recipients were seronegative before HSCT. None developed CMV infection or CMV-specific immunity. A total of 17 recipients were seropositive: (i) four patients spontaneously controlled CMV. The median of CMVspecific IFNc-secreting CD4 T cells was 9.13/ll at month 3 in these four patients and three of the four patients evidenced optimal proliferative responses since month 1; (ii) in 10 patients who received anti-CMV chemotherapy because of prolonged viremia, lower (P ¼ 0.016) IFNc responses (0.39/ll), together with delayed and/or depressed proliferative responses, were observed; (iii) finally, one patient with early CMV-associated disease had undetectable proliferative and IFNc responses until month 3. In conclusion, both intense IFNc responses and early proliferative responses seem to be associated with optimal CMV control.

Development of Cytomegalovirus and Adenovirus-Specific Memory CD4 T-Cell Functions From Birth to Adulthood

“…In agreement with a previous study (24), a high correlation between CMV-specific IFN␥-secreting CD4 Ͼ0.03% and CMV ϩ serologic status was found in children older than 2 y. Indeed, 20 of 21 children older than 2 y and with a CMV ϩ serostatus evidenced IFN␥ responses to CMV Ͼ0.03%, whereas none with a CMV Ϫ serostatus.…”

“…T-cell proliferation assays were performed as previously described (24). In brief, PBMCs were plated at 10 5 per well, each time in triplicate.…”

Signature profiles of CMV-specific T-cells in patients with CMV reactivation after hematopoietic SCT

“…2,[35][36][37] In light of our data, many studies that have focused on measuring single cytokines and chose IFNg would not have been able to differentiate an inefficient single IFNg response from an efficient master response. 14,15,38 A similar limitation applies to a report by Bunde et al, 39 who reported no correlation between pp65-stimulated CD8 þ T-cells and protection, whereas IE-1 stimulated CD8 þ Tcells correlated with protection. We included both pp65 and IE-1 peptide pools in our stimulation cocktail to show a broad response to CMV Ags.…”

Survey of CMV management in pediatric allogeneic HSCT programs, on behalf of the Inborn Errors, Infectious Diseases and Pediatric Diseases Working Parties of EBMT

“…In the near future, integration of immunological parameter monitoring in the algorithm for CMV monitoring and therapy should change our approach by detecting patients who could spontaneously control CMV infection. 26 All centers that answered to this survey use pre-emptive strategy, including those using prophylactic strategy also for either all or only the high-risk patients. The definition of high-risk patients differs between the centers, either only seronegative donor/seropositive recipient or all D/R pair with at least one positive member.…”

“…23 It is well known that beside anti-CMV, pharmaceutical cells are necessary to prevent or control CMV infection and/or reactivation. Hence, new immunological tools and adoptive cell therapy have raised new options 10,[24][25][26][27] to improve CMV infection detection and outcomes.…”