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This Article Full Text Full Text (PDF) All Versions of this Article: 292/5/H2425    most recent 01197.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Schmidt-Lucke, C. Articles by Dimmeler, S. Search for Related Content PubMed PubMed Citation Articles by Schmidt-Lucke, C. Articles by Dimmeler, S.

Specific recruitment of CD4⁺CD25⁺⁺ regulatory T cells into the allograft in heart transplant recipients

¹Molecular Cardiology, Department of Internal Medicine III, University of Frankfurt, Frankfurt, Germany, ²Division of Clinical Immunology and Allergy, University of Florence, Florence, Italy

Submitted 1 November 2006 ; accepted in final form 9 January 2007

Regulatory T cells (T_reg) migrate into allografts and induce tolerance of the graft. Immunosuppressive T_reg are found among CD4⁺CD25⁺⁺ T cells and specifically express the forkhead/winged transcription factor FOXP3. We hypothesized that activated T cells and T_reg might modulate the ongoing inflammation of the cardiac allograft (CA) and that the chronic inflammatory environment might influence the balance between these distinct cell types. We therefore quantified levels of activated T cells and CD4⁺CD25⁺⁺ T_reg in the cardiac and systemic circulation in heart transplant recipients. To determine the influence of the allograft passage on these cells, transcardiac gradients were evaluated in CA recipients (n = 22) compared with controls (n = 18). Systemic levels of circulating T_reg were significantly lower in CA recipients (8.9 ± 1.3 µl) compared with controls (15.8 ± 1.6 µl; P = 0.002). Similarly, the proportion of T_reg related to the total leukocyte number was significantly lower in CA recipients (P < 0.01). In contrast, systemic levels of circulating activated CD4⁺ T cells and of circulating plasmacytoid dendritic cells were similar in both groups. In transplant patients, numbers of T_reg significantly decreased during transcardiac passage (3.0 ± 0.3 to 2.4 ± 0.3% of CD4⁺ T cells, P < 0.01), and FOXP3⁺ T cells invaded into the allograft. In contrast, numbers of activated CD4⁺ T cells increased during passage through the allograft, even in the presence of effective immunosuppression. In conclusion, numbers of circulating immunosuppressive T_reg are reduced in transplant recipients. Recruitment of T_reg into the cardiac allograft during transcoronary passage may induce graft tolerance during subclinical inflammation potentially influencing allograft vasculopathy.

coronary circulation; chronic inflammation