Induction therapy with Campath-IH, a humanized anti-CD52 monoclonal antibody depleting T and B lymphocytes, has been used in organ transplantation with the final goal of resetting the immune system in order to promote a tolerance-permissive environment and, at the same time, to reduce the need for chronic maintenance immunosuppression. To explore whether thisO may result from the capability of Campath-IH, in association with different maintenance regimens, to promote regulatory T cells (Treg) expansion and to assess whether this may translate into better graft outcomes in the long-term, 21 renal transplant patients receiving Campath-IH induction were randomized to low-dose SRL (n=ll) or low-dose CsA (n=10), both in addition to low-dose mycophenolate mofetil (MMF) as maintenance immunosuppressive therapy and monitored for over 30 month follow-up. SRL-treated Patients showed an important expansion of circulating CD4⁺CD25highFOXP3⁺ Treg that, at one and two years after transplant, were significantly more abundant than in the CsA group. T cells isolated from peripheral blood long-term post-transplant were hyporesponsive to donor alloantigens in both treatment arms. In SRL-, but not CsA-treated patients, hyporesponsiveness was reversed by Treg depletion. T cells from CsA-treated pattients were anergic to donor antigens. Despite higher Treg counts, SRL-treated patients had a faster GFR and RPF decline, more clinical proteinuria, significantly higher tubular C4d staining score and a trend to higher chronic allograft damage index score, compared to CsA-treated patients. There was no significant correlation between Treg counts and any considered outcome variable in the study group as a whole and within each treatment group.

Cell-mediated renal allograft rejection is defined by infiltration of the tubules by activated T cells which can express the aE(CD103)B7 integrin. Whilst this molecule may allow adhesion to E-cadherin expressed by tubular epithelial cells, the potential of intratubular chemokines to activate this adhesive process has not been investigated. Initial studies showed that intratubular T cells can express the chemokine receptor CCR9.

Although much is known about human polyomaviruses, there is a paucity of knowledge of polyomavirus infections in renal transplant recipients (RTPs), particularly those given steroid sparing regimens and transmission of polyomaviruses. BK polyomavirus associated nephropathy (PVAN) is an uncommon complication causing graft failure post transplantation. The role of other polyomaviruses JC, Simian Virus 40, WU, KI and Merkel cell (MCV) is unclear. A prospective longitudinal study was carried out of 112 RTPs given steroid sparing regimens to investigate the presence of polyomaviruses. A second prospective study was undertaken of respiratory samples (n = 1640) submitted for the investigation of respiratory infection. The prevalence and dynamics of polyomavirus infections was studied using real-time multiplex PCR assays, antibody assays using recombinant virus-like particles and sequencing for virus typing and investigation of viral variation. There was no significant difference in prevalence for BKV and JCV infections in RTPs between the control and study treatment groups. Overall, 33% of RTPs were positive for BK viruria, of which 10.7% developed viraemia and 1.8% of these progressed to PVAN; 13.3% were positive for JCV infection and 2.7% for MCV. All samples were negative for SV40, WUV and KIV. No dual BKV and JCV infections were observed, although 8% of RTPs had dual BKV and CMV infection and 3.6% had dual JCV and CMV. There were no variations observed in the NCCR of RTPs with PVAN but duplications were observed during a BKV and JCV infection. Both BKV and JCV infections were acquired early post transplantation, molecular epidemiological studies suggested these were of donor origin. In the second study of children and adults with respiratory symptoms 3.6% were positive for WUV infection, 2.74% for KIV, 0.91 % for MCV and 0.18% for BKV infection. Epidemiology suggests a causative role for WUV but not KIV in respiratory disease.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.