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The Human Leucocyte Differentiation Antigens Workshops (HLDA) have since 1984 provided a forum for the characterization and study of leucocyte surface molecules and antibodies against them. HLDA devised the CD nomenclature, which is sanctioned by IUIS. The HLDA Council reviewed and modified the objectives of HLDA in 2004, and changed the name of the organization to Human Cell Differentiation Molecules (HCDM) to reflect the broader objectives. Workshop studies under the HCDM banner proceeded during 2005 and early 2006, culminating in a meeting in May 2006. At that meeting the Council, acting as Nomenclature Committee, approved a number of new CD designations and changes to some pre-existing CD designations, which are summarized in this report.

CD (cluster of differentiation) Ags are cell surface molecules expressed on leukocytes and other cells relevant for the immune system. CD nomenclature has been universally adopted by the scientific community and is officially approved by the International Union of Immunological Societies and sanctioned by the World Health Organization. It provides a unified designation system for mAbs, as well as for the cell surface molecules that they recognize. This nomenclature was established by the Human Leukocyte Differentiation Antigens Workshops. In addition to defining the CD nomenclature, these workshops have been instrumental in identifying and determining the expression and function of cell surface molecules. Over the past 30 y, the data generated by the 10 Human Leukocyte Differentiation Antigens Workshops have led to the characterization and formal designation of more than 400 molecules. CD molecules are commonly used as cell markers, allowing the identification and isolation of leukocyte populations, subsets, and differentiation stages. mAbs against these molecules have proven to be essential for biomedical research and diagnosis, as well as in biotechnology. More recently, they have been recognized as invaluable tools for the treatment of several malignancies and autoimmune diseases. In this article, we describe how the CD nomenclature was established, present the official updated list of CD molecules, and provide a rationale for their usefulness in the 21st century.

Alterations in the neuro-immune axis contribute toward viscerosensory nerve sensitivity and symptoms in Irritable Bowel Syndrome (IBS). Inhibitory factors secreted from immune cells inhibit cob-rectal afferents in health, and loss of this inhibition may lead to hypersensitivity and symptoms. We aimed to determine the immune cell type(s) responsible for opioid secretion in humans and whether this is altered in patients with IBS. The beta-endorphin content of specific immune cell lineages in peripheral blood and colonic mucosal biopsies were compared between healthy subjects (HS) and IBS patients. Peripheral blood mononuclear cell (PBMC) supernatants from HS and IBS patients were applied to cob-rectal sensory afferent endings in mice with post-inflammatory chronic visceral hypersensitivity (CVH). beta-Endorphin was identified predominantly in monocyte/macrophages relative to T or B cells in human PBMC and colonic lamina propria. Monocyte derived beta-endorphin levels and colonic macrophage numbers were lower in IBS patients than healthy subjects. PBMC supernatants from healthy subjects had greater inhibitory effects on cob-rectal afferent mechanosensitivity than those from IBS patients. The inhibitory effects of PBMC supernatants were more prominent in CVH mice compared to healthy mice due to an increase in mu-opioid receptor expression in dorsal root ganglia neurons in CVH mice. Monocyte/macrophages are the predominant immune cell type responsible for beta-endorphin secretion in humans. IBS patients have lower monocyte derived beta-endorphin levels than healthy subjects, causing less inhibition of colonic afferent endings. Consequently, altered immune function contributes toward visceral hypersensitivity in IBS. Refereed/Peer-reviewed

The physiological importance of cytokines and other factors which control cell and tissue growth and differentiation is widely appreciated. While physiological studies have included the cellular receptors for these factors, studies on their role in disease have concentrated on the measurement of cytokines themselves or soluble receptor components. This reflects in part the technical difficulty of measuring cell surface expression of receptors, which occur at and are functional at very low concentrations. In this review, the potential va lue of surface-expressed receptors as markers of disease is assessed, and methods are described which allow measurements with standard equipment for flow cytometry and tluorescence microscopy.

Kohler and Milstein’s1 description of monoclonal antibodies (mAbs) in 1975 revolutionised immunology. With the advent of hybridoma technology, immunologists started to produce an ever increasing number of mAbs directed against leukocyte cell-surface molecules. Inevitably, several mAbs produced by different laboratories and given independent names recognised the same molecule. The First International Human Leucocyte Differentiation Antigen (HLDA) Workshop was organised in the early 1980s, and aimed to identify groups of mAbs reacting with a common human cell-surface antigen and to agree a nomenclature that would facilitate better communication amongst the scientific community.2 The outcomes of the Workshops are the ‘CDs’, an abbreviation for the non-descriptive ‘cluster of differentiation’ number. The CD number is assigned to a group or cluster of mAbs that recognise a molecule expressed on the surface of human leukocytes and other cells relevant to the immune system. The nomenclature has been universally adopted by the scientific community, officially approved by the International Union of Immunological Societies and sanctioned by WHO. Its usage has now evolved and is also commonly used to name the molecules themselves. However, by adding either mAb or molecule/protein it should be made clear whether one means the CDxx mAb or CDxx molecule. Ten HLDA Workshops have been organised to date, with the most recent one held in 2014 in conjunction with the Australasian Society of Immunology in Wollongong, Australia.

The peptidase inhibitor PI16 was shown previously by microarray analysis to be over-expressed by CD4-positive/CD25-positive Treg compared with CD4-positive/CD25-negative Th cells. Using a monoclonal antibody to the human PI16 protein, we found that PI16-positive Treg have a memory (CD45RO-positive) phenotype and express higher levels of FOXP3 than PI16-negative Treg. PI16-positive Treg are functional in suppressor assays . in vitro with potency similar to PI16-negative Treg. Further phenotyping of the PI16-positive Treg revealed that the chemokine receptors CCR4 and CCR6 are expressed by more of the PI16-positive/CD45RO-positive Treg compared with PI16-negative/CD45RO-positive Treg or Th cells. PI16-positive Treg showed enhanced . in vitro migration towards the inflammatory chemokines CCL17 and CCL20, suggesting they can migrate to sites of inflammation. We conclude that PI16 identifies a novel distinct subset of functional memory Treg which can migrate to sites of inflammation and regulate the pro-inflammatory response at those sites. Refereed/Peer-reviewed

A highl y-sen sitile tlourescence method, capable of detecting cytokine receptors present at low concentrations (around I DO molecules per cell) by flow cytometry, was adapted for use on tissue sections. This method was used to examine the expression of several cytokine receptors in lymphoid ti ss ues. lL-2 receptors were distributed broadly, with higher concentrations in T cell areas. lL-1 receptor Type I was detected in T cell areas and in the follicular mantle, and was strongly expressed on vasc ular endothelium. IL-6 receptor was found at very low concentration, both within and outside germinal centres. The gp 130 molecule, which is involved in the functional receptor complex for IL-6 and several other cytokines, was present at higher concentrations, particularly in the germinal centre. Analysis of receptor expression in secondary lymphoid tissue provides evidence bearing on the physiological roles of cytokines, as these tissues contain cells at various stages of physiological activation located in well-defined functional zones.

Adult stem cells are capable of generating all of the cells of the hematopoietic system, and this process is orchestrated in part by the interactions between these cells and the stroma. T cell progenitors emerge from the stem cell compartment and migrate to the thymus, where their terminal differentiation and maturation occur, and it is during this phase that selection shapes the immune repertoire. Notch ligands, including Delta-like 1 (DL1), play a critical role in this lymphoid differentiation. To mimic this in vitro, stroma-expressing DL1 have been used to generate CD4+CD8+ double-positive and single-positive T cells from hematopoietic stem/progenitor cells. This system provides a robust tool to investigate thymopoiesis; however, its capacity to generate regulatory T cells (Tregs) has yet to be reported. Natural Tregs (nTregs) develop in the thymus and help maintain immune homeostasis and have potential clinical use as a cell therapy for modulation of autoimmune disease or for transplant tolerization. Here, we describe for the first time the development of a population of CD4+CD25+ CD127loFoxP3+ cells that emerge in coculture of cord blood (CB) CD34+ progenitors on OP9-DL1 stroma. These hematopoietic progenitor-derived CD4+CD25+ Tregs have comparable suppressor function with CB nTregs in vitro. The addition of IL-2 to the coculture enhanced the expansion and survival of this population significantly. This manipulable culture system, therefore, generates functional Tregs and provides a system to elucidate the mechanism of Treg development.

The immune system works through leukocytes interacting with each other, with other cells, with tissue matrices, with infectious agents, and with other antigens. These interactions are mediated by cell-surface glycoproteins and glycolipids. Antibodies against these leukocyte molecules have provided powerful tools for analysis of their structure, function, and distribution. Antibodies have been used widely in hematology, immunology, and pathology, and in research, diagnosis, and therapy. The associated CD nomenclature is commonly used when referring to leukocyte surface molecules and antibodies against them. It provides an essential classification for diagnostic and therapeutic purposes. The most recent (8th) Workshop and Conference on Human Leukocyte Differentiation Antigens (HLDA), held in Adelaide, Australia, in December 2004, allocated 95 new CD designations and made radical changes to its aims and future operational strategy in order to maintain its relevance to modern human biology and clinical practice.

The process of categorizing the antigenic molecules and epitopes associated with human white cells, via the collaborative study of monoclonal antibodies, dates back to the early 1980s, when the first HLDA (Human Leucocyte Differentiation Antigen) Workshop was held in Paris. This initial meeting