Abstract
Analysis of human cytomegalovirus (HCMV) primary infection in immunocompetent (n=40) and immunocompromised transplant patients (n=20) revealed that the median peak antibody titre neutralizing infection of epithelial cells was 16-fold higher in immunocompromised patients. The mechanism of this finding was investigated by measuring: (i) HCMV DNAemia; (ii) HCMV neutralizing antibodies; (iii) ELISA IgG antibody titre to HCMV glycoprotein complexes gHgLpUL128L, gHgLgO and gB; and (iv) HCMV-specific (IFN-γ+) CD4+ and CD8+ T-cells. Circulating CXCR5+ CD4+ (memory T follicular helper – TFH-cells) were identified as activated TFH (ICOS+PD-1++CCR7lo) and quiescent cells. In the early stages of primary infection, activated TFH cells increased in number. Concomitantly, both neutralizing and IgG antibodies to HCMV glycoproteins reached a peak, followed by a plateau. A stop in antibody rise occurred upon appearance of HCMV-specific CD4+ T-cells, HCMV clearance and progressive reduction in activated TFH cells. The main differences between healthy and transplant patients were that the latter had a delayed DNA peak, a much higher DNA load and delayed activated TFH cells and antibody peaks. Similar events were observed in clinically severe HCMV reactivations of transplant patients. A preliminary analysis of the specificity of the activated TFH cell response to viral proteins showed a major response to the pentamer gHgLpUL128L and gB. In conclusion, in the absence of T-cell immunity, one of the first lines of defence, during primary infection, is conferred by antibodies produced through the interaction of TFH cells and B-cells of germinal centres, resulting in differentiation of B-cells into antibody producing plasma cells.
| Original language | English |
|---|---|
| Article number | 000488 |
| Pages (from-to) | 1928-1941 |
| Number of pages | 14 |
| Journal | Journal of General Virology |
| Volume | 97 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 1 2016 |
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Keywords
- Antibody response
- Human cytomegalovirus
- Immunocompetent
- Immunocompromised patient
- Primary HCMV infection
- TFHcells
ASJC Scopus subject areas
- Medicine(all)
- Virology
Cite this
Follicular helper T-cells and virus-specific antibody response in primary and reactivated human cytomegalovirus infections of the immunocompetent and immunocompromised transplant patients. / Bruno, Francesca; Fornara, Chiara; Zelini, Paola; Furione, Milena; Carrara, Elena; Scaramuzzi, Lucia; Cane, Ilaria; Mele, Federico; Sallusto, Federica; Lilleri, Daniele; Gerna, Giuseppe.
In: Journal of General Virology, Vol. 97, No. 8, 000488, 01.08.2016, p. 1928-1941.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Follicular helper T-cells and virus-specific antibody response in primary and reactivated human cytomegalovirus infections of the immunocompetent and immunocompromised transplant patients
AU - Bruno, Francesca
AU - Fornara, Chiara
AU - Zelini, Paola
AU - Furione, Milena
AU - Carrara, Elena
AU - Scaramuzzi, Lucia
AU - Cane, Ilaria
AU - Mele, Federico
AU - Sallusto, Federica
AU - Lilleri, Daniele
AU - Gerna, Giuseppe
PY - 2016/8/1
Y1 - 2016/8/1
N2 - Analysis of human cytomegalovirus (HCMV) primary infection in immunocompetent (n=40) and immunocompromised transplant patients (n=20) revealed that the median peak antibody titre neutralizing infection of epithelial cells was 16-fold higher in immunocompromised patients. The mechanism of this finding was investigated by measuring: (i) HCMV DNAemia; (ii) HCMV neutralizing antibodies; (iii) ELISA IgG antibody titre to HCMV glycoprotein complexes gHgLpUL128L, gHgLgO and gB; and (iv) HCMV-specific (IFN-γ+) CD4+ and CD8+ T-cells. Circulating CXCR5+ CD4+ (memory T follicular helper – TFH-cells) were identified as activated TFH (ICOS+PD-1++CCR7lo) and quiescent cells. In the early stages of primary infection, activated TFH cells increased in number. Concomitantly, both neutralizing and IgG antibodies to HCMV glycoproteins reached a peak, followed by a plateau. A stop in antibody rise occurred upon appearance of HCMV-specific CD4+ T-cells, HCMV clearance and progressive reduction in activated TFH cells. The main differences between healthy and transplant patients were that the latter had a delayed DNA peak, a much higher DNA load and delayed activated TFH cells and antibody peaks. Similar events were observed in clinically severe HCMV reactivations of transplant patients. A preliminary analysis of the specificity of the activated TFH cell response to viral proteins showed a major response to the pentamer gHgLpUL128L and gB. In conclusion, in the absence of T-cell immunity, one of the first lines of defence, during primary infection, is conferred by antibodies produced through the interaction of TFH cells and B-cells of germinal centres, resulting in differentiation of B-cells into antibody producing plasma cells.
AB - Analysis of human cytomegalovirus (HCMV) primary infection in immunocompetent (n=40) and immunocompromised transplant patients (n=20) revealed that the median peak antibody titre neutralizing infection of epithelial cells was 16-fold higher in immunocompromised patients. The mechanism of this finding was investigated by measuring: (i) HCMV DNAemia; (ii) HCMV neutralizing antibodies; (iii) ELISA IgG antibody titre to HCMV glycoprotein complexes gHgLpUL128L, gHgLgO and gB; and (iv) HCMV-specific (IFN-γ+) CD4+ and CD8+ T-cells. Circulating CXCR5+ CD4+ (memory T follicular helper – TFH-cells) were identified as activated TFH (ICOS+PD-1++CCR7lo) and quiescent cells. In the early stages of primary infection, activated TFH cells increased in number. Concomitantly, both neutralizing and IgG antibodies to HCMV glycoproteins reached a peak, followed by a plateau. A stop in antibody rise occurred upon appearance of HCMV-specific CD4+ T-cells, HCMV clearance and progressive reduction in activated TFH cells. The main differences between healthy and transplant patients were that the latter had a delayed DNA peak, a much higher DNA load and delayed activated TFH cells and antibody peaks. Similar events were observed in clinically severe HCMV reactivations of transplant patients. A preliminary analysis of the specificity of the activated TFH cell response to viral proteins showed a major response to the pentamer gHgLpUL128L and gB. In conclusion, in the absence of T-cell immunity, one of the first lines of defence, during primary infection, is conferred by antibodies produced through the interaction of TFH cells and B-cells of germinal centres, resulting in differentiation of B-cells into antibody producing plasma cells.
KW - Antibody response
KW - Human cytomegalovirus
KW - Immunocompetent
KW - Immunocompromised patient
KW - Primary HCMV infection
KW - TFHcells
UR - http://www.scopus.com/inward/record.url?scp=84985994878&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84985994878&partnerID=8YFLogxK
U2 - 10.1099/jgv.0.000488
DO - 10.1099/jgv.0.000488
M3 - Article
AN - SCOPUS:84985994878
VL - 97
SP - 1928
EP - 1941
JO - Journal of General Virology
JF - Journal of General Virology
SN - 0022-1317
IS - 8
M1 - 000488
ER -