Cytomegalovirus - Specific cellular imunity: Profile of immune function assesment provides clinically relevant answer
Abstract
Introduction: Effective immune response, mediated by T-cells in particular, is necessary to control CMV infection. Children after hematopoietic stem cell transplantation (HSCT) are highly vulnerable to repeated, often life-threatening CMV infections, due to secondary immunodeficiency caused by conditioning regimens.
Methods: We examined peripheral blood mononuclear cells of 57 healthy volunteers and 10 patients two or more years after HSCT for CMV antigen evoked ex vivo T-cell responses. We compared responses between CMV positive and CMV negative donors.
We also compared responses among the CMV-positive children, adults and patients recovered two or more years after HSCT. Measurement of intracellular cytokines (IFN-γ and IL-2), activation molecule CD154 (CD40L), a marker of degranulation (CD107a) allowed us to define different subsets of CD4+ and CD8 + T-cell responses using multicolor flow cytometry.
Results: We found following subsets relevant for CMV control by comparing CMV seropositive and seronegative volunteers among CD4+ T-cells: IFN-γ+/CD40L+ and IFN-γ+/IL-2+/CD40L+. There were also five relevant populations among CD8+ T-cells: IFN-γ+/ IL-2+/CD107a+/CD40L+, IFN-γ+/IL-2+/CD40L+, IFN-γ+/IL2+, IFN-γ+/CD40L+ and IFN-γ+.
When comparing children's and adult healthy donors to patients 2 or more years after HSCT with fully restored immunity, we found no statistically significant differences, thus CMV specific immunity is fully restored after HSCT. Finally, we demonstrate comparison of the immune function profile of patients at risk of reactivation with those with fully restored immunity.
Conclusion: In conclusion, ex vivo testing of CMV specific T-cell immune responses is a valuable tool for immune monitoring of patients after HSCT and complements the already established method of CMV viral load monitoring using quantitative PCR.