Influence of immunosuppressive drugs on the development of CD4(+)CD25(high) Foxp3(+) T cells in liver transplant recipients.
BACKGROUND
Many studies suggest that CD4(+)CD25(high) T regulatory cells (Tregs) have a crucial role in downregulating the immune response to alloantigens. In this study, we investigated the possible influence of immunosuppressive therapy, including rapamycin and calcineurin inhibitors (CNIs; tacrolimus), on level of Tregs in liver allograft recipients.


METHODS
We assessed 47 liver transplant recipients with stable liver function for ≥2 years, dividing them into 2 groups: Patients receiving rapamycin (n = 15), and those receiving tacrolimus (n=32). Thirty-eight, age-matched healthy subjects were used as normal controls. We examined the expression of CD4, CD25, and Foxp3 in peripheral blood T cells. Flow cytometry was performed with a FACSCalibur instrument with data analysis using Cell Quest software.


RESULTS
Rapamycin significantly increased the prevalence of Tregs, including the percentage of CD4(+)CD25(high) T cells in total lymphocytes and among total CD4(+) T cells, compared with the healthy subjects and the CNI group. The prevalence of Tregs in the CNIs group was significantly lower than that of controls. Foxp3 was expressed in >95% of CD4(+)CD25(high)T cells, whereas it was in <20% of CD4(+)CD25(low) T cells and not expressed among CD4(+)CD25(-) T cells.


CONCLUSIONS
Immunosuppressive therapy (rapamycin or CNIs) may have a different roles in tolerance induction among liver transplant recipients. Namely, rapamycin promoted the induction of a profile consistent with alloantigen tolerance; CNIs hampered this progression.
Chu
Z
Z
The First Hospital of China Medical University, Shenyang, China.
Zhang
J
J
Zhao
Y
Y
Ji
Q
Q
Zhong
J
J
Zhang
C
C
Zhang
B
B
D015704:CD4 Antigens / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry / Q000379:methods; D051858:Forkhead Transcription Factors / Q000097:blood / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood / Q000276:immunology*; D016031:Liver Transplantation / Q000276:immunology*; D012016:Reference Values; D020123:Sirolimus / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016559:Tacrolimus / Q000627:therapeutic use
D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D020123:Sirolimus; D016559:Tacrolimus