2nd Conference of the Robert A. Good immunology society primary immune deficiencies and immune reconstitution Harvard Me
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2nd Conference of the Robert A. Good immunology society primary immune deficiencies and immune reconstitution Harvard Medical Boston, November 16th, 17th Luigi Notarangelo Æ Noorbibi Day Æ Thomas Fleisher
Published online: 2 May 2009 Ó Springer Science+Business Media, LLC 2009
In the 1950s, Robert A. Good and his team made a series of seminal discoveries that helped to identify the distinct—yet essential—role that the thymus and equivalents of the bursa of Fabricius in chicken have for development of cell-mediated and humoral immunity in many species, including man [1]. Dr. Good’s group had performed a series of experiments in rabbits and mice that showed the neonatal thymectomy affects not only the development of cell-mediated and anti-tumor immunity, but also the ability to mount vigorous antibody responses to what we now define T-dependent antigens [2]. Similar data on the critical role of the thymus were shared by other groups at a conference that Dr. Good organized in Minneapolis in 1962 [3]. DiGeorge syndrome was soon thereafter identified as the prototypic condition in humans in which impaired thymus development is associated with an increased occurrence of infections of viral and fungal origin, and reduced antibody production in spite of preserved immunoglobulin serum levels [4]. These discoveries led to the first attempts to achieve immune reconstitution in DiGeorge syndrome by thymus transplantation (Cleveland v 219) and in infants with SCID. Furthermore, Dr. Good postulated that the two major specific cellular components of immunity that are missing in infants with SCID could be presumed to descend from bone marrow-derived lymphoid cells, and that therefore, it should be possible to cure SCID by bone marrow transplantation. Indeed, hematopoietic cell transplantation (HCT) was successfully applied for the first time in humans in 1968, when Dr. Good and his team treated an infant with X-linked severe combined immunodeficiency (X-SCID) with intraperitoneal injection of bone marrow cells from his sister who has a single antigen mismatch at the HLA-A locus [5]. This experience confirmed Dr. Good’s hypothesis and opened the way for the use of HCT in the treatment of a variety of congenital and acquired human disorders. Perhaps less known is the fact that the first successful experience of HCT in humans was at the same time illustrative of some of the most significant complications of HCT. In particular, acute graft versus host disease (GvHD) due to mismatching at the HLA-A locus, was observed, that was solved upon a boosting bone marrow injection of L. Notarangelo (&) N. Day T. Fleisher Department of Pediatrics and Pathology, Havard Medical School, The Manton Center for Orphan Disease Research, and Division of Immunology, Children’s Hospital Boston, Karp Family Research Building, 9th Floor, Room 9210, 1 Blackfan Circle, Boston, MA 02115, USA e-mail: [email protected]
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Immunol Res (2009) 44:1–3
bone marrow cells from the same donor. Moreover, initial immune reconstitution was char
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