Differential kinetics of effector and regulatory T cells in patients on calcineurin inhibitor-based drug regimens.
Besides iatrogenic immunosuppression, endogenous suppression by regulatory T cells (Tregs) may also mediate inhibition of effector T cells after transplantation. Here we determined the effect of common immunosuppressive drug regimens on both Treg and effector T cells. Tregs and cytomegalovirus (CMV)-specific T cells were quantified in 88 renal transplant recipients, 58 hemodialysis patients, and 22 controls. T cell dynamics were longitudinally assessed within 20 weeks after transplantation. The number of Tregs was quantified by measurement of CD25 and/or FOXP3-positive cells and by functional assays. CMV-specific T cells were quantified by stimulation-induced intracellular cytokine analysis. Treg frequencies in transplant recipients were significantly lower compared to those in hemodialysis patients and controls. These lower Treg levels were associated with a less pronounced suppression of effector function. Treg levels decreased within the first weeks after transplantation and remained low in the long term. In contrast, although decreased at early post-transplant, long-term levels of CMV-specific T cells normalized to levels found in hemodialysis patients and controls. These studies suggest that there is an initial decrease of Tregs and effector T cells as a consequence of a direct inhibitory effect of immunosuppressive drugs. In the long term, persistently low Treg levels may favor normalization of effector T cells to ensure sufficient pathogen control.
Presser
Daniela
D
Department of Internal Medicine IV, University of the Saarland, Homburg D-66421, Germany.
Sester
Urban
U
Mohrbach
Janine
J
Janssen
Martin
M
Köhler
Hans
H
Sester
Martina
M
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D065095:Calcineurin Inhibitors; D003587:Cytomegalovirus / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D016030:Kidney Transplantation / Q000276:immunology*; D007700:Kinetics; D008137:Longitudinal Studies; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
D065095:Calcineurin Inhibitors; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D007371:Interferon-gamma