Basiliximab versus rabbit antithymocyte globulin as induction therapy for living-related renal transplantation: a single-center experience.

PURPOSE: To compare the long-term effects of the interleukin-2 receptor antagonist basiliximab versus rabbit antithymocyte globulin as an induction therapy for living-related renal transplantation. METHODS: This is a prospective, open-label, nonrandomized, controlled study including 213 cases of renal transplant. Immunosuppressive therapy containing calcineurin inhibitors, mycophenolate mofetil and steroids was applied in all cases. The interleukin-2 receptor antagonist group (IL2Ra group) included 108 cases with 20 mg basiliximab induction on Day 0 and Day 4. The other 105 cases comprised the rabbit antithymocyte globulin group (rATG group) with 1.0 mg/kg/day ATG induction from Day 0 to Day 4. The primary endpoint was biopsy-proven acute rejection. Other endpoints included delayed graft function (DGF), graft loss and death. RESULTS: All patients were followed up for 3 years. Acute rejection rates in the IL2Ra group and the ATG group were 5.6 and 3.8 % (P = 0.781), and the differences in the DGF rates, graft loss and death were insignificant between groups. All-cause infection rates in the IL2Ra and rATG groups were 26.9 and 43.8 % (P = 0.010). Urinary tract infections were more common in the rATG group than in the IL2Ra group (15.2 vs 6.5 %, P = 0.040). Specific viral infection rates were significantly different (18.1 % in rATG group vs 8.3 % in IL2Ra group, P = 0.035). CONCLUSIONS: IL2Ra and rATG had no significant differences as induction therapies during the perioperative period of living-related renal transplantation, according to acute rejection rates, DGF rates, graft loss, 1- and 3-year patient/graft survival rates. However, the incidence of infection, especially of urinary tract infection and specific viral infection, was higher in rATG-induced patients.

Gene therapy improves immune function in preadolescents with X-linked severe combined immunodeficiency.

Retroviral gene therapy can restore immunity to infants with X-linked severe combined immunodeficiency (XSCID) caused by mutations in the IL2RG gene encoding the common gamma chain (gammac) of receptors for interleukins 2 (IL-2), -4, -7, -9, -15, and -21. We investigated the safety and efficacy of gene therapy as salvage treatment for older XSCID children with inadequate immune reconstitution despite prior bone marrow transplant from a parent. Subjects received retrovirus-transduced autologous peripherally mobilized CD34(+) hematopoietic cells. T-cell function significantly improved in the youngest subject (age 10 years), and multilineage retroviral marking occurred in all 3 children.

Niveles de interleucina-2 y su receptor soluble en pacientes operados y transfundidos / Interleukin-2 levels and its soluble receptor in operated on and transfused patients

Se realizó un estudio aleatorio para determinar los niveles de interleucina-2 (IL-2) y su receptor soluble (RsIL-2) en pacientes operados y transfundidos, antes de la cirugía, en el hemoderivado y 24 h después de la transfusión y para relacionar los niveles de IL-2 y RsIL-2 con cada período. Mediante inmunoensayo enzimático se determinaron los niveles de de IL-2 y RsIL-2 en 40 pacientes operados, antes de la cirugía, en los derivados sanguíneos y 24 horas después de la transfusión. Se obtuvieron valores promedio de 3,98 U/mL; 3,18 U/mL e indetectable para IL-2 y de de 678,2; 1 402 y 90,34 pg/mL para RsIL-2, en los períodos respectivos. El declive de la función linfocitaria después de cirugía y transfusión se atribuye a cambios intrínsecos o a la redistribución de células T reactivas de la sangre hacia los tejidos, a factores séricos como prostaglandinas y corticoesteroides, inhibidores de IL-2 que, con los elevados valores de RsIL-2 hallados en la bolsa, explican los niveles indetectables de IL-2 a las 24 horas de la transfusión(AU)

He/she was carried out an aleatory study to determine the interleucina-2 levels (IL-2) and their soluble receiver (RsIL-2) in operated patients and transfused, before the surgery, in the hemoderivado and 24 h after the transfusion and to relate the levels of IL-2 and RsIL-2 with every period. By means of enzymatic inmunoensayo the levels were determined of of IL-2 and RsIL-2 in 40 operated patients, before the surgery, in those derived sanguine and 24 hours after the transfusion. Values average of 3,98 U/mL were obtained; 3,18 U/mL and indetectable for IL-2 and of of 678,2; 1 402 and 90,34 pg/mL for RsIL-2, in the respective periods. The decline of the function linfocitaria after surgery and transfusion is attributed to intrinsic changes or the redistribution of cells T you reactivate of the blood toward the fabrics, to factors séricos like prostaglandinas and corticoesteroides, inhibitors of IL-2 that, with the high values of RsIL-2 found in the bag, they explain the levels indetectables of IL-2 at the 24 hours of the transfusion(AU)

Alloantigen-induced CD25+CD4+ regulatory T cells can develop in vivo from CD25-CD4+ precursors in a thymus-independent process.

The capacity of naturally occurring autoreactive CD25+CD4+ regulatory T cells (Treg) to control immune responses both in vivo and in vitro is now well established. It has been demonstrated that these cells undergo positive selection within the thymus and appear to enter the periphery as committed CD25+CD4+ Treg. We have shown previously that CD25+CD4+ Treg with the capacity to prevent skin allograft rejection can be generated by pretreatment with donor alloantigen under the cover of anti-CD4 therapy. Here we demonstrate that this process does not require an intact thymus. Furthermore, generation of these Treg is not dependent on the expansion of CD25+CD4+ thymic emigrants, because depletion of CD25+ cells before pretreatment does not prevent Treg development, and Treg can be generated from CD25-CD4+ precursors. Taken together, these results clearly demonstrate that CD25+CD4+ Treg can be generated in the periphery from CD25-CD4+ precursors in a pathway distinct to that by which naturally occurring autoreactive CD25+CD4+ Treg develop. These observations may have important implications for the design of protocols, both experimental and clinical, for the induction of tolerance to autoantigens or alloantigens in adults with limited thymic function.

Selective blockade of IL-15 by soluble IL-15 receptor alpha-chain enhances cardiac allograft survival.

IL-15 is a T cell growth factor that shares many functional similarities with IL-2 and has recently been shown to be present in tissue and organ allografts, leading to speculation that IL-15 may contribute to graft rejection. Here, we report on the in vivo use of an IL-15 antagonist, a soluble fragment of the murine IL-15R alpha-chain, to investigate the contribution of IL-15 to the rejection of fully vascularized cardiac allografts in a mouse experimental model. Administration of soluble fragment of the murine IL-15R alpha-chain (sIL-15Ralpha) to CBA/Ca (H-2k) recipients for 10 days completely prevented rejection of minor histocompatibility complex-mismatched B10.BR (H-2k) heart grafts (median survival time (MST) of >100 days vs MST of 10 days for control recipients) and led to a state of donor-specific immunologic tolerance. Treatment of CBA/Ca recipients with sIL-15Ralpha alone had only a modest effect on the survival of fully MHC-mismatched BALB/c (H-2d) heart grafts. However, administration of sIL-15Ralpha together with a single dose of a nondepleting anti-CD4 mAb (YTS 177.9) delayed mononuclear cell infiltration of the grafts and markedly prolonged graft survival (MST of 60 days vs MST of 20 days for treatment with anti-CD4 alone). Prolonged graft survival was accompanied in vitro by reduced proliferation and IFN-gamma production by spleen cells, whereas CTL and alloantibody levels were similar to those in animals given anti-CD4 mAb alone. These findings demonstrate that IL-15 plays an important role in the rejection of a vascularized organ allograft and that antagonists to IL-15 may be of therapeutic value in preventing allograft rejection.