SttnaryTransplantation of HLA mismatched hematopoietic stem cells in patients with severe combined immunoddiciency (SCID) can result in a selective engraftment of T cells of donor origin with complete immunologic reconstitution and in vivo tolerance. The latter may occur in the absence of clonal deletion of donor T lymphocytes able to recognize the host HLA antigens. The activity of these host-reactive T cells is suppressed in vivo, since no graft-vs.-host disease is observed in these human chimeras. Here it is shown that the CD4 + host-reactive T cell clones isolated from a SCID patient transplanted with fetal liver stem cells produce unusually high quantities ofinterleukin 10 (IL-10) and very low amounts of IL-2 after antigen-specific stimulation in vitro. The specific proliferative responses of the host-reactive T cell clones were considerably enhanced in the presence of neutralizing concentrations of an anti-IL-10 monodonal antibody, suggesting that high levels of endogenous IL-10 suppress the activity of these cells. These in vitro data correlate with observations made in vivo. Semi-quantitative polymerase chain reaction analysis carried out on freshly isolated peripheral blood mononuclear cells (PBMC) of the patient indicated that the levels of IL-10 messenger KNA (mRNA) expression were strongly enhanced, whereas IL-2 mKNA expression was much lower than that in PBMC of healthy donors. In vivo IL-10 mRNA expression was not only high in the T cells, but also in the non-T cell fraction, indicating that host cells also contributed to the high levels of IL-10 in vivo. Patient-derived monocytes were found to be major IL-10 producers. Although no circulating IL-10 could be detected, freshly isolated monocytes of the patient showed a reduced expression of class II HLA antigens. However, their capacity to stimulate T cells of normal donors in primary mixed lymphocyte cultures was within the normal range. Interestingly, similar high in vivo IL-10 mKNA expressions in the T and non-T cell compartment were also observed in three SCID patients transplanted with fetal liver stem cells and in four SCID patients transplanted with T cell-depleted haploidentical bone marrow stem cells. Taken together, these data indicate that high endogenous IL-10 production is a general phenomenon in SCID patients in whom allogeneic stem cell transplantation results in immunologic reconstitution and induction of tolerance. Both donor T cells and host accessory cells contribute to these high levels of IL-10, which would suppress the activity of host-reactive T cell in vivo. GVHD remains the major clinical problem after allogeneic hematopoietic stem cell transplantation (1-3).

Survival of perinatally HIV-infected children improved in 1996-1998 as a result of the introduction of combined antiretroviral therapies. JAMA. 2000;284:190-197

To estimate the risk of mother-to-child transmission of hepatitis C virus (HCV) and identify correlates of transmission, 245 perinatally exposed singleton children followed prospectively beyond 18 months of age were studied. Overall, 28 (11.4%) of the 245 children acquired HCV infection. Transmission occurred in 3 of 80 children (3.7%) whose mothers had HCV infection alone and in 25 of 165 (15.1%; P õ .01) whose mothers had concurrent infection with human immunodeficiency virus type 1 (HIV-1). The percentage of HIV-1-infected children was similar (22 of 165, 13.3%), but each virus was transmitted independently; only six infants (3.6%) were coinfected with HCV and HIV-1. The risk of HCV transmission was not associated with maternal HIV-1-related symptoms, intravenous drug use, prematurity, low birth weight, or breast-feeding, whereas it was lower with cesarean section than with vaginal delivery (5.6% vs. 13.9%, P Å .06). This suggests that transmission occurs mainly around the time of delivery.birth weight, mode of delivery, and type of feeding were also Mother-to-child transmission of hepatitis C virus (HCV) is investigated. widely documented. However, in different investigations the estimated risk of infection ranged from zero to 100% [1 -15]. This variability derives from differences in methods used toPatients and Methods define the child's infection status, duration of follow-up, and size and features of the populations studied.Patients. A cohort of 245 children born to HCV-infected Transmission of HCV may occur in utero via the transplacenwomen were enrolled at 12 participating centers. In three cental route at any time during pregnancy, at the time of delivery, ters all parturients were screened for HCV-seropositivity; in and postnatally through breast-feeding. Several factors might the remaining centers, HCV testing was mostly performed only favor or hamper infection of the offspring. Identification of for women who had a history of IVDU or were known to be these factors would allow the adoption of rational preventive HIV-1-infected. Only singleton at-risk infants identified within strategies and the offer of specific counseling, but little is the first 2 weeks of life and followed up for at least 18 months known about the timing and correlates of transmission. High were included in this study. levels of viremia [5 -7], certain HCV genotypes [8], and materData collection. Specific information was collected by nal coinfection with HIV-1 [1, 2, 4, 7, 9, 15] have been associquestionnaire on maternal risk factors for HCV infection ated with increased HCV transmission rates, although the re-(IVDU, transfusions, sexual contact with an infected partner, sults are controversial [10 -13]; breast milk does not seem to other, unknown), mother's HIV-1 infection status at delivery have a significant role [13 -15].(presence or absence of specific antibody), length of pregnancy The aim of this study was to quantitate the risk of HCV (weeks), mode of delivery (vaginal, elective/emergency cesarinfection in children born to...

The worldwide prevalence of hepatitis C virus (HCV) infection in children is 0.05%-0.4% in developed countries and 2%-5% in resource-limited settings, where inadequately tested blood products or un-sterile medical injections still remain important routes of infection. After the screening of blood donors, mother-to-child transmission (MTCT) of HCV has become the leading cause of pediatric infection, at a rate of 5%. Maternal HIV co-infection is a significant risk factor for MTCT and anti-HIV therapy during pregnancy seemingly can reduce the transmission rate of both viruses. Conversely, a high maternal viral load is an important, but not preventable risk factor, because at present no anti-HCV treatment can be administered to pregnant women to block viral replication. Caution is needed in adopting obstetric procedures, such as amniocentesis or internal fetal monitoring, that can favor fetal exposure to HCV contaminated maternal blood, though evidence is lacking on the real risk of single obstetric practices. Mode of delivery and type of feeding do not represent significant risk factors for MTCT. Therefore, there is no reason to offer elective caesarean section or discourage breast-feeding to HCV infected parturients. Information on the natural history of vertical HCV infection is limited. The primary infection is asymptomatic in infants. At least one quarter of infected children shows a spontaneous viral clearance (SVC) that usually occurs within 6 years of life. IL-28B polymorphims and genotype 3 infection have been associated with greater chances of SVC. In general, HCV progression is mild or moderate in children with chronic infection who grow regularly, though cases with marked liver fibrosis or hepatic failure have been described. Non-organ specific autoantibodies and cryoglobulins are frequently found in children with chronic infection, but autoimmune diseases or HCV associated extrahepatic manifestations are rare.

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