BACKGROUND: To reduce the side effects of long-term immunosuppressive therapy, stable renal transplant patients were routinely converted from cyclosporine to either azathioprine or mycophenolate mofetil. Thereafter, the azathioprine and mycophenolate mofetil dose was reduced to 75% at 4 months and to 50% at 8 months after conversion. We questioned whether the T-cell reactivity before conversion was able to predict which patients could be safely converted and tapered in their immunosuppressive load, while remaining free from acute rejection. METHODS: Before conversion, the T-cell reactivity of peripheral blood mononuclear cells against donor and third-party spleen cells were tested in mixed lymphocyte cultures. We measured the frequency of donor and third-party reactive helper T-lymphocyte (HTLpf) and cytotoxic T-lymphocyte (CTLpf) precursors and their avidity for HLA class I antigens using limiting dilution analysis. Peripheral blood mononuclear cells were also stimulated with tetanus toxoid to test the general immune response. RESULTS: The tetanus toxoid response, reactivity to donor and third-party cells as measured in mixed lymphocyte cultures and HTLpf, and the avidity of cytotoxic T-lymphocyte precursors were not predictive for the development of acute rejection. However, significant differences were found in donor-specific CTLpf before conversion, between patients with and without acute rejection after conversion in immunosuppression. The donor-specific CTLpf was significantly lower in patients without compared to those with acute rejection (P=0.01). Additionally, when no CTLpf was detectable before conversion, acute rejection did not occur after conversion. Acute rejection was only diagnosed in patients with detectable CTLpf before conversion. CONCLUSION: The number of donor-specific cytotoxic T-lymphocytes identifies patients in whom the immunosuppressive load can be safely reduced.
BACKGROUND: To reduce the side effects of long-term immunosuppressive therapy, stable renal transplant patients were routinely converted from cyclosporine to either azathioprine or mycophenolate mofetil. Thereafter, the azathioprine and mycophenolate mofetil dose was reduced to 75% at 4 months and to 50% at 8 months after conversion. We questioned whether the T-cell reactivity before conversion was able to predict which patients could be safely converted and tapered in their immunosuppressive load, while remaining free from acute rejection. METHODS: Before conversion, the T-cell reactivity of peripheral blood mononuclear cells against donor and third-party spleen cells were tested in mixed lymphocyte cultures. We measured the frequency of donor and third-party reactive helper T-lymphocyte (HTLpf) and cytotoxic T-lymphocyte (CTLpf) precursors and their avidity for HLA class I antigens using limiting dilution analysis. Peripheral blood mononuclear cells were also stimulated with tetanus toxoid to test the general immune response. RESULTS: The tetanus toxoid response, reactivity to donor and third-party cells as measured in mixed lymphocyte cultures and HTLpf, and the avidity of cytotoxic T-lymphocyte precursors were not predictive for the development of acute rejection. However, significant differences were found in donor-specific CTLpf before conversion, between patients with and without acute rejection after conversion in immunosuppression. The donor-specific CTLpf was significantly lower in patients without compared to those with acute rejection (P=0.01). Additionally, when no CTLpf was detectable before conversion, acute rejection did not occur after conversion. Acute rejection was only diagnosed in patients with detectable CTLpf before conversion. CONCLUSION: The number of donor-specific cytotoxic T-lymphocytes identifies patients in whom the immunosuppressive load can be safely reduced.
Authors: Rob J Rentenaar; Jelle L G Vosters; Frank N J van Diepen; Ester B M Remmerswaal; René A W van Lier; Ineke J M ten Berge Journal: Immunology Date: 2002-03 Impact factor: 7.397
Authors: P J E J van de Berg; S L Yong; S D Koch; N Lardy; K A M I van Donselaar-van der Pant; S Florquin; F J Bemelman; R A W van Lier; I J M ten Berge Journal: Clin Exp Immunol Date: 2012-05 Impact factor: 4.330
Authors: N M van Besouw; J M Zuijderwijk; L M B Vaessen; A H M M Balk; A P W M Maat; P H van der Meide; W Weimar Journal: Clin Exp Immunol Date: 2005-09 Impact factor: 4.330
Authors: N M van Besouw; B J van der Mast; P de Kuiper; P J H Smak regoor; Lenard M B Vaessen; J N M Ijzermans; T van Gelder; W Weimar Journal: Clin Exp Immunol Date: 2002-05 Impact factor: 4.330
Authors: Sabrina M Hess; Ellen F Young; Keith R Miller; Benjamin G Vincent; Adam S Buntzman; Edward J Collins; Jeffrey A Frelinger; Paul R Hess Journal: Transpl Immunol Date: 2013-10-23 Impact factor: 1.708
Authors: Ellen Kreijveld; Hans J P M Koenen; Bram van Cranenbroek; Esther van Rijssen; Irma Joosten; Luuk B Hilbrands Journal: PLoS One Date: 2008-07-16 Impact factor: 3.240