Differences in CMV-specific T-cell levels and long-term susceptibility to CMV infection after kidney, heart and lung transplantation.
Patients after kidney, heart and lung transplantation differ in their immunosuppressive drug regimens and in susceptibility to infectious complications with cytomegalovirus (CMV). In this study, CMV-specific T-cell responses were characterized in long-term transplant recipients and associated with the frequency of infectious complications. CMV-reactive CD4 T cells from 50 healthy controls, 68 renal, 14 heart and 24 lung transplant recipients were flow cytometrically quantified by the induction of cytokines after specific stimulation. Moreover, the immunosuppressive effect of calcineurin inhibitors on specific T-cell reactivity was quantified in vitro and compared with responses in vivo. Median CMV-specific T-cell frequencies in long-term renal (1.48%; range 0.06-17.26%) and heart transplant recipients (0.90%; 0.13-12.49%) did not differ from controls (1.82%; 0.26-21.00%). In contrast, CMV-specific T-cell levels were significantly lower in lung transplant recipients (0.50%; <0.05-4.98%) and showed a significant correlation with the frequency of infectious episodes (r =-0.57, p = 0.005). The differences within the groups were associated with increasing dosages of immunosuppressive drugs, as exemplified for calcineurin inhibitors that dose dependently reduced specific T-cell reactivity in vitro. In conclusion, monitoring CMV-specific CD4 T cells may serve as a measure for long-term disease susceptibility and may contribute to an improved management of CMV complications after lung transplantation.
Sester
Urban
U
Medical Department IV, University of the Saarland, Homburg, Germany.
Gärtner
Barbara C
BC
Wilkens
Heinrike
H
Schwaab
Bernhard
B
Wössner
Rolf
R
Kindermann
Ingrid
I
Girndt
Matthias
M
Meyerhans
Andreas
A
Mueller-Lantzsch
Nikolaus
N
Schäfers
Hans-Joachim
HJ
Sybrecht
Gerhard W
GW
Köhler
Hans
H
Sester
Martina
M
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D065095:Calcineurin Inhibitors; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000276:immunology / Q000517:prevention & control*; D004198:Disease Susceptibility; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects*; D016040:Lung Transplantation / Q000009:adverse effects*; D008875:Middle Aged; D013997:Time Factors; D019562:Viral Load
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents