Immune Tolerance and Alloreactivity in Liver Transplant Recipients on Different Monotherapy Immunosuppressive Agents

Summary

This study is being done with the purpose of trying to understand if and why transplant recipients may develop tolerance to their transplanted organ. Tolerance means being able to lower or take away immunosuppression (anti-rejection medications) without causing organ rejection.

Conditions

• Liver Transplant Rejection
• Immunosuppression

Interventions

PROCEDURE

Blood Draw - Rapamycin

Ten calcineurin-inhibitors (CNI) monotherapy or dual therapy (CNI+MMF) patients will have blood taken (40 ml=8 tsp.) 2 wks. prior to conversion, 3-6 months post successful conversion. 1) Regulatory/Suppressor Cells (CD4+CD25+FOXP3+CD127low; and CD8+ CD28-FOXP3+CD127low cells). 2) Dendritic cell assays: myeloid vs. lymphoid (CD11c; CD123); maturation and ability to process antigens (CD83; CD205); markers shown to induce regulatory T cells (ILT3; ILT4), 3) Soluble HLA G, and 4) Liver function/drug levels. If problems develop during conversion (e.g. acute rejection, significant drug side effects) requiring discontinuation of rapamycin, MMF and/or reversion to CNI therapy, assays will not be performed. Monthly liver function/drug levels performed after successful conversion (standard of care).

PROCEDURE

Blood Draw from Control Subjects

Ten healthy individuals will have blood drawn (40 ml = 8 teaspoons (tsps.)).Blood will be drawn at one time point for the following: * Dendritic cell assays: myeloid vs. lymphoid (CD11c; CD123); maturation and ability to process antigens (CD83; CD205); markers that have been shown to induce regulatory T cells (ILT3; ILT4). * Regulatory/Suppressor Cells (CD4+CD25+FOXP3+CD127low; and CD8+ CD28- FOXP3+CD127low cells). * HLA microchimerism \& HLA G

PROCEDURE

Blood Draw - CyA

Blood drawn from 10 patients on cyclosporine (CyA) (40 ml = 8 tsp.)). Blood will be drawn at one time point for the following: * Dendritic cell assays: myeloid vs. lymphoid (CD11c; CD123); maturation and ability to process antigens (CD83; CD205); markers that have been shown to induce regulatory T cells (ILT3; ILT4). * Regulatory/Suppressor Cells (CD4+CD25+FOXP3+CD127low; and CD8+ CD28- FOXP3+CD127low cells). * HLA microchimerism \& HLA G

PROCEDURE

Blood Draw - Tacrolimus

Blood drawn from 5 patients on Tacrolimus (40 ml = 8 tsp.) at one time point for the following: * Dendritic cell assays: myeloid vs. lymphoid (CD11c; CD123); maturation and ability to process antigens (CD83; CD205); markers that have been shown to induce regulatory T cells (ILT3; ILT4). * Regulatory/Suppressor Cells (CD4+CD25+FOXP3+CD127low; and CD8+ CD28- FOXP3+CD127low cells). * HLA microchimerism \& HLA G

PROCEDURE

Blood Draw - MMF

Blood will be drawn from 10 patients on mycophenolate mofetil (MMF) (40 ml or the equivalent of 8 teaspoons). Blood will be drawn at one time point for the following analysis: * Dendritic cell assays: myeloid vs. lymphoid (CD11c; CD123); maturation and ability to process antigens (CD83; CD205); markers that have been shown to induce regulatory T cells (ILT3; ILT4). * Regulatory/Suppressor Cells (CD4+CD25+FOXP3+CD127low; and CD8+ CD28- FOXP3+CD127low cells). * HLA microchimerism \& HLA G

PROCEDURE

Blood Draw - Rapamycin

Blood drawn from 10 patients on rapamycin (40 ml = 8 tsp.)) at one time point for the following: * Dendritic cell assays: myeloid vs. lymphoid (CD11c; CD123); maturation and ability to process antigens (CD83; CD205); markers that have been shown to induce regulatory T cells (ILT3; ILT4). * Regulatory/Suppressor Cells (CD4+CD25+FOXP3+CD127low; and CD8+ CD28- FOXP3+CD127low cells). * HLA microchimerism \& HLA G

Sponsors & Collaborators

• Northwestern Memorial Hospital

  collaborator OTHER

• Northwestern University

  lead OTHER

Principal Investigators

• Josh Levitsky, MD · Northwestern University, Northwestern Memorial Hospital, Northwestern Medical Faculty Foundation

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2007-09-30

Primary Completion

2008-05-31

Completion

2008-09-30

Countries

• United States

Study Locations