RESUMEN
Donor-reactive memory T (Tm)cells mediate accelerated rejection, which is known as a barrier to the survival of transplanted organs. Selective interference with the anti-CD45RB monoclonal antibody (α-CD45RB) reliably induces donor-specific tolerance. In this study, pre-sensitization to female C57BL/6 mice with the skin of female BLAB/c mice generated a large number of Tm cells and resulted in rapid rejection of the secondly transplanted allografts. α-CD45RB did induce the tolerance to skin allograft primarily transplanted but failed to induce tolerance in the pre-sensitized mice. Donor-specific spleen cell transfusion (DST) alone also failed to induce the tolerance in the pre-sensitized recipients. Interestingly, combination of α-CD45RB with DST inhibited the rejection induced by memory T cells in the pre-sensitized mice. CD25+ T-cell depletion in α-CD45RB combined with DST therapy recipients could prevent skin allograft tolerance from establishing. In addition, adoptive transfer of donor-primed memory T cells into the tolerant recipients markedly broke the established tolerance. Our findings indicate that α-CD45RB and DST can synergistically inhibit the accelerated rejection mediated by memory T cells and induce long-term skin allograft acceptance in mice.
Asunto(s)
Aloinjertos/inmunología , Rechazo de Injerto/inmunología , Memoria Inmunológica , Antígenos Comunes de Leucocito/metabolismo , Trasplante de Piel , Bazo/citología , Linfocitos T/inmunología , Donantes de Tejidos , Animales , Apoptosis , Proliferación Celular , Femenino , Supervivencia de Injerto/inmunología , Inflamación/patología , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Depleción Linfocítica , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Análisis de Supervivencia , Linfocitos T Reguladores/inmunologíaRESUMEN
XPG gene contributes to DNA repair defects and genomic instability, which may lead to the initiation of uterine leiomyoma. We hypothesized that genetic variants of XPG gene may alter the carriers' susceptibility to leiomyoma. The association between five potential functional single nucleotide polymorphisms (SNPs), i.e. rs2094258 C>T, rs751402 C>T, rs2296147 T>C, rs1047768 T>C, rs873601 G>A, and uterine leiomyoma risk in Chinese, was investigated in this case-control study, which included 398 incident leiomyoma cases and 733 controls. We found that rs873601 was significantly associated with tumor risk in a recessive genetic model after being adjusting for age and menopause. When compared with rs873601 GG/GA genotypes, the AA genotype had an increased leiomyoma risk (adjusted OR = 1.59, 95% CI = 1.16-2.18, P=0.004; Bonferroni adjusted P=0.040). Furthermore, stratified analysis revealed that the association between the rs873601 AA genotype and leiomyoma risk was more evident among subjects younger than 40 years old (adjusted OR = 1.58, 95% CI = 1.06-2.35, P=0.023) and patients who had more than three myomas (adjusted OR = 2.05, 95% CI = 1.24-3.41, P=0.006). Yet, no significant association between the other four polymorphisms and leiomyoma risk was observed. To sum up, the present study reported on the association between XPG gene polymorphisms and myoma risk. The observed data indicated that SNP rs873601 G>A contributes to uterine leiomyoma susceptibility in a Southern Chinese population.
Asunto(s)
Proteínas de Unión al ADN/genética , Endonucleasas/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Leiomioma/genética , Proteínas Nucleares/genética , Factores de Transcripción/genética , Adulto , Alelos , China/epidemiología , Reparación del ADN/genética , Femenino , Genotipo , Humanos , Leiomioma/patología , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Factores de RiesgoRESUMEN
Islet transplantation offers hope for patients with type 1 diabetes, which is an autoimmune disease. However, islet transplant recipients must overcome two obstacles in both allograft rejection and autoimmune reaction. Alpha-1-antitrypsin (a1-proteinase inhibitor, AAT) possesses anti-inflammatory properties, reduces cytokine-mediated islet damage, and induces specific immune tolerance. In this study, an insulinoma cell line, NIT-1, was transfected with human AAT (hAAT), named NIT-hAAT, and was transplanted to the left renal subcapsular spaces of 7-week-old female non-obese diabetic (NOD) mice (n=22). Cyclophosphamide(CY) was administered to synchronize and accelerate the development of diabetes. Thus, the immunosuppressive and cytoprotective activity of hAAT in ß-cell transplantation was investigated. NIT-hAAT has immunomodulatory properties, which delay the onset of autoimmune diabetes, reduce diabetes incidence, inhibit insulitis and ß-cell apoptosis, and dampen transplant site inflammation. We propose that NIT-hAAT has a dual function by improving islet autoimmunity and protecting transplanted ß-cells from allograft rejection. However, the low expression of hAAT in vivo results in the inability of NIT-hAAT to induce long-term specific immune tolerance and to completely block allograft rejection.