The mechanisms responsible for the low-level regeneration of CD4(+) cells involve, at least, deficiency in the regeneration of central CD4(+) cells and excessive apoptosis.
Mutations of the AML1 gene are frequent molecular abnormalities in minimally differentiated acute myeloblastic leukemia (M0 AML), a rare type of AML. In this retrospective multicenter study, morphologic, immunophenotypical, cytogenetic, and molecular features of 59 de novo M0 AML cases were analyzed and correlated to AML1 mutations. Point mutations of AML1 gene were observed in 16 cases (27%). They were correlated with higher white blood cell (WBC) count (P ؍ .001), greater marrow blast involvement (P ؍ .03), higher incidence of immunoglobulin H/T-cell receptor (IgH/TCR) gene rearrangement (P < .0001), and with a borderline significant lower incidence of complex karyotypes. In the 59 patients, FLT3 mutations were the only significant prognostic factors associated with short sur-
Graft failure remains a severe complication of hematopoietic stem cell transplantation (HSCT). Several risk factors have already been published. In this study, we re-evaluated them in a large cohort who had the benefit of the recent experience in HSCT (2006-2012). Data from 4684 unrelated donor HSCT from 2006 to 2012 were retrospectively collected from centers belonging to the French Society for Stem Cell Transplantation. Among the 2716 patients for whom HLA typing was available, 103 did not engraft leading to a low rate of no engraftment at 3.8%. In univariate analysis, only type of disease and status of disease at transplant for malignant diseases remained significant risk factors (P=0.04 and P<0.0001, respectively). In multivariate analysis, only status of disease was a significant risk factor (P<0.0001). Among the 61 patients who did not engraft and who were mismatched for 1 HLA class I and/or HLA-DP, 5 donor-specific antibodies (DSAs) were detected but only 1 was clearly involved in graft failure, for the others their role was more questionable. Second HSCT exhibited a protective although not statistically significant effect on OS (hazard ratio=0.57 [0.32-1.02]). In conclusion, only one parameter (disease status before graft) remains risk factor for graft failure in this recent cohort.
Primary infection with cytomegalovirus (CMV) in immunocompetent hosts is accompanied with activation and differentiation of naive CD8ϩ T cells to effector/memory cells secreting interferon-␥ (IFN-␥). Alteration of these responses during the perinatal period is suggested by a higher rate of CMV diseases in congenital infection. For addressing this issue, immunologic investigations were performed in 15 fetuses (22-36 wk of gestation) with documented congenital CMV infection. Results show that cellular immune responses can be detected as soon as the 22nd week of gestation (the youngest fetus analyzed). Compared with age-matched control subjects, infected fetuses evidence a dramatic increase in the percentages of activated and terminally differentiated CD8 T cells. Indeed, median percentages (interquartile range) of HLA-DR ϩ and of CD28 Ϫ CD8 ϩ T cells were 24% (19 -34) and 38% (24 -52), respectively in infected fetuses versus 3% (0 -4) for each subset in control subjects. In addition, the percentages of T cells secreting IFN-␥ after in vitro stimulation with phorbol myristate acetate and
CD8ϩ T lymphocytes are believed to be an important host defense against viruses. This concept is supported by the fact that patients with defects in cellular immunity experience more prolonged virus shedding and present more frequent and severe illness with cytomegalovirus (CMV) (1, 2). Furthermore, viral immunity to CMV can be restored by the adoptive transfer of CMV-specific CD8 ϩ T cells in immunodeficient individuals (3).During primary infection with CMV, CD8 ϩ T cells are activated, proliferate, and differentiate to become effector and memory lymphocytes. Effector/memory CD8 ϩ T cells possess cytotoxic activity. In addition, they become capable of releasing factors with antiviral action, such as interferon-␥ (IFN-␥) (4). Activation and differentiation of CD8 ϩ T cells during viral infection are associated with changes in the cell surface phenotype. In persistent virus infections, HLA-DR expression on CD8 ϩ T cells reflects immune activation (5). Also, during the course of infection, part of CD8 T cells switch progressively to a long-lived CD8 ϩ CD28 Ϫ T-cell pool (6), which contains virus-specific, cytolytic T lymphocytes (7,8). It has been suggested that these CD28 Ϫ CD8 ϩ T cells might be terminally differentiated because of their poor proliferative potential (9).The great majority of primary CMV infections in immunocompetent hosts are clinically silent, whereas the rate of CMV disease is 10 -15% in congenital infection (10). This difference is supposed to be related to the immaturity of the immune system. The concept of immaturity of CD8 ϩ T-cell functional responses to viruses has been largely documented in mouse models (11,12) and also suggested in the human. As an example, the incidence of children who are younger than 6 mo of age and develop CD8 T-cell activities, as measured by cytotoxicity (13, 14) or IFN-␥ secretion (15)
QuantiFERON-TB Gold In-Tube performance was evaluated in 19 French immunocompetent children (0.29-5.36 years; median: 1.52) with active tuberculosis. The rate of indeterminates results was 0/19 and the rates of positivity were 6/10 and 9/9 in <2 and 2- to 5-year-old children, respectively. QuantiFERON-TB Gold In-Tube in association with tuberculin skin test could improve diagnosis of tuberculosis even in young children.
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