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The expression of interleukin 7 receptor alpha(high) (IL-7Ralpha(high)) discriminates between activated CD25(+)CD45RO(+)CD4(+) T cells [IL-7Ralpha(high) and forkhead box P3-negative (FoxP3(-))] and regulatory T cells (IL-7Ralpha(low) and FoxP3(+)). The IL-7Ralpha(high)CD25(+)CD45RO(+)CD4(+)FoxP3(-) T cell population has been shown to be expanded in the blood and tissues of patients after kidney transplantation and to contain alloreactive T cells (activated T cells). In the present study, we analyzed the distribution of IL-7Ralpha(high)CD25(+)CD45RO(+)CD4(+)FoxP3(-) T cells in the blood of 53 patients after liver transplantation. The IL-7Ralpha(high)CD25(+)CD45RO(+)CD4(+)FoxP3(-) T cell population was significantly expanded (P < 0.0001) in stable transplant recipients versus healthy donors. However, the magnitude of the expansion was significantly higher (P < 0.0001) in liver transplant recipients with no hepatitis C virus (HCV) infection in comparison with those with a preexisting HCV infection. Interestingly, effective suppression of HCV viremia after antiviral therapy was associated with an increase in the IL-7Ralpha(high)CD25(+)CD45RO(+)CD4(+)FoxP3(-) T cell population to levels comparable to those of liver transplant recipients not infected with HCV. The present results indicate that (1) the IL-7Ralpha(high)CD25(+)CD45RO(+)CD4(+)FoxP3(-) T cell population is expanded after liver transplantation, (2) it is a valuable immunological marker for monitoring activated and potential alloreactive CD4 T cells in liver transplantation, and (3) a preexisting HCV infection negatively influences the expansion of this population in liver transplant recipients.

Sirolimus (SRL) has been proposed to replace calcineurin inhibitors (CNI) in case of CNI-induced toxicity. The aim of this study was to evaluate the efficacy and safety of conversion from CNI to SRL in maintenance liver transplantation (LT) patients. Between 2002 and 2006, conversion was performed in 48 patients (17 female, 31 male; mean age 57 +/- 10 yr) after a median delay of 19.4 months (range 0.2-173 months) after LT. Indication for conversion was renal impairment (RI) (78%), CNI neurotoxicity (13%), or post-LT cancer (9%). Median follow-up was 22.6 +/- 11 months. Median SRL dosage and trough levels were 2.4 +/- 1.3 mg and 8.1 +/- 2.7 microg/L. Immunosuppression consisted of SRL alone (33%), or SRL + mycophenolate mofetil (MMF) (39%), SRL + prednisone (15%), SRL + CNI (4%), or SRL + MMF + prednisone (8%). Mean glomerular filtration rate (GFR) improved from 33 to 48 mL/minute in patients with severe RI (P = 0.022) and from 56 to 74 mL/minute in patients with moderate RI (P = 0.0001). After conversion, main complications were albuminuria (36%), hyperlipidemia (49%), dermatitis (14%), edema (14%), oral ulcers (12%), joint pain (4%), infection (2%), and pneumonia (2%). Acute rejection (AR) occurred in 17% of the patients. SRL was withdrawn in 17% of the patients. In conclusion, conversion from CNI to SRL is safe and is associated with significant renal function improvement.

Microchimerism (MC) is defined by the persistence of <1% circulating donor cells resulting from cell migration from the graft; MC may play a role in the induction of unresponsiveness to allogeneic tissues, or may be merely the consequence of the graft's acceptance following immunosuppression. To analyze early MC (7 patients) and late MC (12 patients) following a liver transplantation, we designed a sensitive and semiquantitative nested polymerase chain reaction (PCR) protocol based on the detection of incompatible human leukocyte antigen (HLA)-DRB1 donor alleles. MC was measured in multiple PCR samples and expressed as percent positive PCRs / time point. The detection level was 1 donor cell / 10(5) patient cells. All patients had detectable early MC, ranging from 5 to 100% positive PCRs in the 1st 3 months after transplantation. The kinetic analysis demonstrated that MC decreased during the 1st year in 6 of 7 patients. All of the 4 patients with the lowest MC had rejection episodes, vs. none among the 3 patients with MC >50%. However, cytotoxic T-lymphocyte reactivity (CTL) against HLA class I donor antigens could be demonstrated 1 year posttransplant in 2 patients with a high level of early MC. MC is a dynamic process, which is easily detectable <3 months after liver transplantation. In conclusion, a correlation between the level of early MC and the absence of rejection episodes was observed. However, high levels of early MC did not abrogate the persistence of an alloreactive response measured in vitro 1 year after transplantation, which suggests that MC did not lead to clonal deletion of donor-specific CTL.