Graft-versus-host disease (GVHD), a major complication after allogeneic transplantation, can be abrogated by the Campath (anti-CD52) monoclonal antibody. The induction of acute GVHD requires host antigens to be presented to donor T cells by antigen-presenting cells (APCs). Recent evidence has suggested that only host APCs can interact with donor T cells in the induction of GVHD. Because CD52 has been reported to be expressed on DCs, we reasoned that pretransplant Campath-1G might have a direct effect on circulating DCs in addition to any effects on donor T cells. Using direct immunostaining, we demonstrated expression of CD52 on DCs and that Campath-1G killed purified DCs in vitro. In vivo Campath also depleted DCs. Twenty-four hours after the first dose of Campath-1G, circulating DCs were reduced by a mean of 79% (range, 44%-96%). By day 0 after 5 doses of Campath-1G and chemoradiotherapy conditioning, DCs became undetectable in 7 of 9 cases, whereas in 6 of 7 patients receiving conditioning therapy without Campath-1G, host DCs were still detectable. The reconstitution of circulating DCs after transplantation was not affected by Campath-1G and in both groups DC1 (CD11c ؉ ) recovered more rapidly than DC2 (CD11c ؊ ). Analysis of chimerism confirmed that the DCs recovering after transplantation in patients receiving Campath-1G were of donor origin. We conclude that in vivo Campath-1G causes a rapid depletion of host circulating DCs and that this may, in part, explain the low incidence of acute GVHD. The reconstitution of donor DCs was not delayed, which may be important in preserving immune reconstitution. IntroductionHigh-dose chemoradiotherapy followed by the allogeneic transplantation of hematopoietic stem cells from either bone marrow (BM) or peripheral blood stem cells (PBSCs) is widely used in the treatment of malignant and nonmalignant hematologic diseases. However, allogeneic transplantation is frequently associated with the development of acute graft-versus-host disease (GVHD), which is thought to occur as a result of donor T-cell activation damaging host tissues particularly affecting the liver, skin, and gastrointestinal tract. 1,2 Current therapeutic approaches to the prevention of acute GVHD after transplantation include immunosuppression with agents such as cyclosporin and methotrexate. However, despite these measures GVHD still remains a significant cause of morbidity and mortality. [3][4][5] Alternative strategies for the prevention of acute GVHD have focused on the depletion of donor T cells from the graft before infusion into the host. [6][7][8] Although it has been recognized for many years that T-cell depletion decreases the risk of GVHD development, 6,9 it also increases the risk of leukemia relapse in chronic myeloid leukemia 10 and graft rejection. 11 A number of different approaches to T-cell depletion have been used including CD34 ϩ cell selection 12,13 and ex vivo treatment of the graft with monoclonal antibodies. For this purpose, Campath-1M, which recognizes the CD52 antigen, has been...

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Background There are limited data on the immune profiles of HIV-positive children, compared with healthy controls, and no such data for Asian children. Objectives To immunophenotype HIV-positive Asian children, including long-term non-progressors (LTNPs), compared with age-matched healthy controls. Methods We used flow cytometry to analyze 13 lymphocyte and monocyte subsets from 222 untreated, HIV-positive children with 15%–24% CD4+ T cells and no AIDS-related illnesses and 142 healthy children (controls). Data were compared among age categories. Profiles from LTNPs (n=50), defined as children≥ 8 years old with CD4+ T-cell counts ≥ 350 cells/mm3, were compared with data from age-matched non-LTNPs (n=17) and controls (n=53). Results Compared with controls, HIV-positive children had lower values (cell count per mm3 and percent distribution) for helper T cells and higher values for cytotoxic T cells, with reductions in populations of naïve helper and cytotoxic T cells, B cells, and natural killer (NK) cells. HIV-positive children had high values for activated helper and cytotoxic T cells. Compared with non-LTNPs, LTNPs had higher values of helper and cytotoxic T cells, naïve and memory T-cell subsets, and B and NK cells. Surprisingly, counts of activated helper and cytotoxic T cells were also higher among LTNPs. LNTPs were more frequently male. Conclusions Untreated, HIV-infected Asian children have immune profiles that differ from those of controls, characterized by low values for helper T cells, naive T cells, B cells, and NK cells but high values for cytotoxic, activated helper, and cytotoxic T cells. The higher values for activated T cells observed in LTNPs require confirmation in longitudinal studies. Clinical Implications The distinct immunologic profile of LTNPs might identify lymphocyte subsets associated with HIV disease progression.

Infantile malignant autosomal recessive osteopetrosis (ARO; OMIM 259700) has been reported to be associated with mutations in TCIRG1, CLCN7, or OSTM1. ARO caused by homozygous (or compound heterozygous) mutations in CLCN7, as described here, is usually diagnosed at birth or early in infancy due to generalized osteosclerosis and severe hematologic deficits. The maximal life expectancy of patients with ARO in the absence of bone marrow transplantation is thought to be 10 years. We report on a 25-year-old Thai man who is affected with ARO. Clinical features include proportionate short stature, vision impairment, esotropia, exophthalmos, mild hearing loss, and hepatosplenomegaly. Pancytopenia was present and the patient had frequent illnesses. Radiographs showed generalized osteosclerosis with almost no visible of bone marrow spaces. Dense maxilla and mandible with impacted and malformed teeth were observed. Multiple fractures were reported. He developed osteomyelitis of the mandible on four separate occasions, and partial mandibulectomy was performed. Molecular studies showed that there were no pathogenic mutations in TCIRG1. However, mutation analysis of CLCN7 revealed a homozygous missense mutation (p.Arg526Gln). This patient is, it appears, the longest lived individual with ARO ever reported. Evaluation of osteoclastogenesis in our patient demonstrated very large immature osteoclasts with a high number of nuclei.