RESUMO
The phenomenon of tolerance to noninherited maternal Ags (NIMA) is poorly understood. To analyze the NIMA effect C57BL/6 (H-2(b/b)) males were mated with B6D2F(1) (H-2(b/d)) females, whereby 50% of the offspring are H-2(b/b) mice that have been exposed to maternal H-2(d) alloantigens. Controls were H-2(b/b) offspring of C57BL/6 mothers, either inbred C57BL/6 mice or F(1) backcross mice from breedings with H-2(b/d) fathers. We found that 57% of the H-2(b/b) offspring of semiallogeneic (H-2(b/d)) mothers accepted fully allogeneic DBA/2 (H-2(d/d)) heart grafts for >180 days, while similar transplants were all rejected by day 11 in controls (p < 0.0004). Foster nursing studies showed that both oral and in utero exposure to NIMA are required for this tolerogenic effect. An effect of NIMA was also found to extend the survival of skin grafts from a semiallogeneic donor (p < 0.02). Pretransplant analysis of splenocytes showed a 40-90% reduction of IL-2-, IL-5-, and IFN-gamma-producing T cells responding to H-2(d)-expressing APC in NIMA(d)-exposed vs control mice. Injection of pregnant BALB/c-dm2 (H-2L(d)-negative) female mice i.v. with H-2L(d)(61-80) peptide profoundly suppressed the offspring's indirect pathway alloreactive CD4(+) T cell response to H-2L(d). These results suggest that the natural exposure of the fetus and newborn to maternal cells and/or soluble MHC Ags suppresses NIMA-allospecific T cells of the offspring, predisposing to organ transplant tolerance in adult mice.
Assuntos
Antígenos H-2/imunologia , Tolerância Imunológica , Troca Materno-Fetal/imunologia , Animais , Animais Recém-Nascidos/imunologia , Vasos Coronários/transplante , Cruzamentos Genéticos , Feminino , Feto/imunologia , Facilitação Imunológica de Enxerto/métodos , Sobrevivência de Enxerto/genética , Sobrevivência de Enxerto/imunologia , Antígenos H-2/administração & dosagem , Antígenos H-2/genética , Transplante de Coração/imunologia , Transplante de Coração/patologia , Antígeno de Histocompatibilidade H-2D , Tolerância Imunológica/genética , Imunoglobulina G/biossíntese , Injeções Intravenosas , Masculino , Troca Materno-Fetal/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/imunologia , Gravidez , Transplante de Pele/imunologia , Subpopulações de Linfócitos T/imunologiaRESUMO
A direct comparison of the inhibitory effects of alpha, beta, and gamma interferons (IFNs) on replication of a hepatitis C virus subgenomic replicon in a hepatoma cell line revealed similarities in antiviral potency. However, alternate IFN-induced antiviral mechanisms were suggested following observations of striking differences between IFN-gamma and IFN-alpha/beta with respect to strength and durability of the antiviral response and the magnitude and pattern of IFN-mediated gene expression.
