TY - JOUR
T1 - Polyfunctional Analysis of Human Cytomegalovirus (HCMV)-Specific CD4+ and CD8+ Memory T-Cells in HCMV-Seropositive Healthy Subjects Following Different Stimuli
AU - Gabanti, Elisa
AU - Bruno, Francesca
AU - Fornara, Chiara
AU - Bernuzzi, Stefano
AU - Lilleri, Daniele
AU - Gerna, Giuseppe
PY - 2014/11/5
Y1 - 2014/11/5
N2 - Purpose: Following primary human cytomegalovirus (HCMV) infection, both humoral and T-cell-mediated immune responses develop in immunocompetent subjects. However, while antibodies may be measured by different methodologies, the T-cell-mediated response remains to be analyzed in its polyfunctional aspects, in view of defining (following different stimuli) the optimal assay to monitor the HCMV-specific T-cell response in HCMV-seropositive subjects.Methods: In a group of 30 HCMV-seropositive adults, T-cell response revealed by the HCMV-infected dendritic cell (iDC) stimulus was compared with those given by the HCMV-infected cell lysate (iCL), and by a 34-peptide pool (PP).Results: All HCMV-seropositive subjects showed presence of both HCMV-specific CD4+ and CD8+ T-cells in peripheral blood following iDC stimulation. One subject did not respond to PP. As compared to iDC, the number of HCMV-specific stimulated T-cells/μl blood was slightly lower for iCL (P = 0.195) and significantly lower for PP (P = 0.001). Polyfunctional analysis of the T-cell response indicated that the lower number of CD4+ T-cells stimulated by iCL was due to the bifunctional (IFN-γ+ TNF-α+) and CD40L-negative T-cell reduction, while the reduction in specific PP-stimulated CD8+ T-cells was attributable to the reduction in tri-(IFN-γ+ TNF-α+ IL2+), bi-(IFN-γ+ TNF-α+) and mono-(IFN-γ+) functional T-cells. In addition, 15/30 (50 %) subjects showed a CD4+ cross-response to PP, and 11/30 (37 %) a CD8+ cross-response to iCL.Conclusions: HCMV-specific stimulus given by iDC is not significantly different from that of iCL on CD4+ and is significantly superior to that of PP on CD8+ T-cells. However, iCL may contribute significantly to CD8+, and PP to CD4+ T-cell stimulation.
AB - Purpose: Following primary human cytomegalovirus (HCMV) infection, both humoral and T-cell-mediated immune responses develop in immunocompetent subjects. However, while antibodies may be measured by different methodologies, the T-cell-mediated response remains to be analyzed in its polyfunctional aspects, in view of defining (following different stimuli) the optimal assay to monitor the HCMV-specific T-cell response in HCMV-seropositive subjects.Methods: In a group of 30 HCMV-seropositive adults, T-cell response revealed by the HCMV-infected dendritic cell (iDC) stimulus was compared with those given by the HCMV-infected cell lysate (iCL), and by a 34-peptide pool (PP).Results: All HCMV-seropositive subjects showed presence of both HCMV-specific CD4+ and CD8+ T-cells in peripheral blood following iDC stimulation. One subject did not respond to PP. As compared to iDC, the number of HCMV-specific stimulated T-cells/μl blood was slightly lower for iCL (P = 0.195) and significantly lower for PP (P = 0.001). Polyfunctional analysis of the T-cell response indicated that the lower number of CD4+ T-cells stimulated by iCL was due to the bifunctional (IFN-γ+ TNF-α+) and CD40L-negative T-cell reduction, while the reduction in specific PP-stimulated CD8+ T-cells was attributable to the reduction in tri-(IFN-γ+ TNF-α+ IL2+), bi-(IFN-γ+ TNF-α+) and mono-(IFN-γ+) functional T-cells. In addition, 15/30 (50 %) subjects showed a CD4+ cross-response to PP, and 11/30 (37 %) a CD8+ cross-response to iCL.Conclusions: HCMV-specific stimulus given by iDC is not significantly different from that of iCL on CD4+ and is significantly superior to that of PP on CD8+ T-cells. However, iCL may contribute significantly to CD8+, and PP to CD4+ T-cell stimulation.
KW - dendritic cells
KW - Human cytomegalovirus
KW - memory T-cells
KW - peptide pool
KW - polyfunctional analysis
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U2 - 10.1007/s10875-014-0093-5
DO - 10.1007/s10875-014-0093-5
M3 - Article
C2 - 25231588
AN - SCOPUS:84911976091
VL - 34
SP - 999
EP - 1008
JO - Journal of Clinical Immunology
JF - Journal of Clinical Immunology
SN - 0271-9142
IS - 8
ER -