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Immunocompetent donor T cells in Allogeneic Haematopoietic Stem Cell grafts mediate acute Graft versus Host Disease (GvHD), still a major cause of recipient morbidity and mortality post transplant. Despite the advent of high resolution HLA-typing and matching at HLA loci, acute GvHD remains a significant problem, even in HLA matched siblings, due primarily to minor histocompatability antigen mismatches. Treatment of GvHD remains ineffective and highly immunosuppressive and the challenge to find effective methods of prevention continues. Non selective removal of donor T cells from the graft has been proven to be effective in preventing GvHD but the beneficial effects of donor T cells, namely effective immune reconstitution and anti tumour activity, are lost. This review considers mechanisms by which acute GvHD may be prevented in the context of the current model of GvHD immunopathogenesis, with a special emphasis on the recent techniques of selective removal or destruction of donor allogeneic T cells that have been described. [ABSTRACT FROM AUTHOR]

The advent of the Code of Practice for Tissue Banks has led to the requirement for quality systems to be established in all laboratories involved in the production or processing of all cellular tissues to be used therapeutically. The quality system is all-encompassing from process validations and quality assurance to the standard of facilities and staff training. This seems self-evident to those working within the transfusion field but is a relatively novel concept to many hospital laboratories preparing transplant products such as bone marrow or peripheral blood derived haematopoietic stem cells. This review places the current guidelines in an historical context and explains many of the central tenets and requirements of the Code of Practice while outlining a process to facilitate preparation for accreditation. [ABSTRACT FROM AUTHOR]

Natural killer cells represent the predominant lymphoid cell in the peripheral blood for many months after allogeneic or autologous stem cell transplant and their role in immunity to pathogens during this period is established. However, following the largely unsuccessful trials of NK and IL-2 activated NK cells for the treatment of haematological malignancies in the 1980's and 90’s, their role in tumour immunology was discredited. Over the past ten years we have come to understand some of the complex regulatory pathways involved in NK cell activation and we are now in a position to capitalise upon this knowledge. This review presents our current state of understanding of NK cell regulation and highlights the role of these cells in engraftment, graft-versus-host disease, anti-leukaemia activity and post-transplant infection. [ABSTRACT FROM AUTHOR]

Low expression of CD45RB on CD45RO+ T lymphocytes defines a subset of highly differentiated T lymphocytes that accumulate in vivo within the affected joints of patients with rheumatoid arthritis (RA). Although it is known that CD45RO+ T lymphocytes migrate to sites of inflammation m vivo, it is not clear whether within this subset the CD45RBlo cells are selectively recruited or develop in situ within the joint. Using a transwell system we show that a small proportion of resting T lymphocytes migrated across unactivated human umbilical vein endothelial cells (HUVEC). These migrating cells were CD45RO+ and enriched for low CD45RB expression. In addition, both the CD45RO+ CD45RBlo subset and migrating cells expressed increased levels of β1 and β2 integrins and CD44. The percentage of CD45RO+ CD45RBlo T lymphocytes was increased in the circulation of patients with acute Epstein-Barr virus (EBV) infection. These in vim activated cells also expressed increased levels βl and β2 integrins and CD44, and showed an enhanced rate of transmigration compared with resting T lymphocytes. Transmigration of T lymphocytes was increased using the chemokines RANTES and lymphotactin and the cytokine interleukin-15 (IL-15). In addition, infection of the HUVEC with cytomegalovirus (CMV) led to an enhanced movement of T lymphocytes. In all of these cases the selective migration of the CD45RBlo subset was maintained. Thus although the rate of T-lymphocyte transmigration could be influenced by a number factors, the CD45RO+ CD45RBlo subset has a migratory advantage suggesting that more differentiated CD45RO+ CD45RBlo T lymphocytes are selectively recruited to sites of inflammation. [ABSTRACT FROM AUTHOR]

Female CBA/H (H-2k, Misb) mice alloimmunized prior to and during syngeneic pregnancy with DBA/2 (H-2d, Misa) splenocytes gave rise to offspring which resisted graft-versus-host disease (GVHD) following neonatal intraperitoneal inoculation of high doses of DBA/2 spleen cells. Lymphocytes from GVHD-resistant mice tested after 6 weeks of age were unresponsive to DBA/2 stimulator cells in 72 h mixed lymphocyte cultures. Isotope uptake measured 24 h after culture, however, indicated that a considerable early response was made to DBA/2 which later declined. Proliferative responses to BALB/c were also depressed but no early response to this strain was detected, FACS analysis of T-lymphocyte profiles of the GVHD-resistant CBA/H mice revealed a 100% increase in the Lyt-2+ subpopulation compared to normal CBA/H mice. Significant increases in Lyt-2+ cells were also noted in in vitro cultures of CBA/H lymphocytes responding to GVHD-resistant CBA/H stimulators. Lymphocytes from GVHD-resistant mice suppressed the proliferative responses of normal CBA/H lymphocytes to alloantigenic but not mitogenic stimulation. Suppression of alloantigenic responses were shown to be specific to DBA/2 and did not affect the response to BALB/c stimulator cells, indicating that both anergy and specific suppressor cells were operative in inducing unresponsiveness. [ABSTRACT FROM AUTHOR]

Comments on the evolution of stem cells and immunotherapy. Development of a method to protect mice against radiation-induced bone marow failure; Quantification of stem cells using clonogenic assays; Concept of stem cell plasticity.

Dendritic cells (DCs) are the most potent antigen-presenting cells described to date. In human peripheral blood, both myeloid and lymphoid subsets of DCs have been identified. In contrast, cord blood (CB) DCs have recently been described as being exclusively of the immature CD11c- lymphoid DC subset. Using an alternative method of enrichment, based on a negative selection system, both lymphoid (HLA-DR+ CD123+++ CD11c- CD33-) and myeloid (HLA-DR++ CD123+ CD11c+ CD33+) DCs were identified in CB. Although the majority of CB DCs showed a lymphoid phenotype, a significant number of CD11c+ myeloid DCs (25.6% +/- 14.5%, n = 13) were also present. Other markers, such as CD80 and CD83, were negative in both subsets. Analyses of the allostimulatory capacity of both subsets showed that freshly isolated CB lymphoid DCs failed to induce a potent allostimulation of naive CB T cells. These features are therefore consistent with previous work reporting an immature phenotype for lymphoid DCs in adult blood. The significance of the inverted CD11c+/CD11c- ratio observed in CB DCs (1:3) with respect to adult blood DCs (3:1) remains to be explained.