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Clinical immunology

linical or medical immunol-ogy is an extremely interest-ing and broad field, trans-lating the achievements of

immunological research to diagnosis and therapy; it is an attractive area for students,however, the conditions for studying and practising clinical immunology vary greatly throughout Europe. The extent of this diversity appears in the results of a poll involving the majority of national im-munology societies in Europe, which can be viewed on the EFIS-CIG site hosted by EFIS in the ?Clinical Immunology? section (https://www.wendangku.net/doc/ea14296828.html,). In addition, a con-sensus commentary has been formulated (also on this website) describing the speci-ficity of clinical immunology. Here, we

provide a summary of these documents.

Scope of clinical immunology in Europe

In countries where thought has been given to the definition of clinical immunology,there seems to be a consensus, which is shared with relevant literature 1D3, to include the following :immunodeficiencies, auto-immune diseases, allergy, transfusion and transplantation, lymphoproliferative disor-ders, immune responses to microbes and cancers, and immunotherapy or therapeutics involving the immune system.

The bedside aspect of clinical immunol-ogy overlaps a number of other medical dis-ciplines, which probably explains why in most countries it has been difficult to clearly differentiate this as a clinical speciality. The situation is clearer for the laboratory side 4,identified as a medical speciality in several countries. Basic immunology is part of the general education at medical schools, but countries vary in the amount of teaching they provide, leaving doctors of medicine (MDs) with very different immunological knowledge within Europe.

T raining in clinical immunology

The training and certification for bedside im-munologists is best organized in Australia 5.In Europe, defined curricula exist or are in preparation with specific requirements both in laboratory and bedside practice in several countries. Training in laboratory immunology is more structured. In most countries, this postgraduate education is associated with research activities, and a PhD in immunol-ogy is required or strongly recommended.Continuing education is seldom considered.The participation of national immunology societies in the development of clinical im-munology is variable, involving the organiz-ation of clinical sessions at national meetings,specific courses, specialized committees or affinity groups, or even full responsibility for training programmes and certification.Supranational societies might have an important role in homogenizing training and professional criteria, taking into account the positive results experienced in some coun-tries, and in view of the recently imple-mented free circulation rules concerning MDs in Europe. A first step in this direction can be seen in the field of accreditation 6,backed by the European Cooperation for Accreditation (EA) and/or the European Con-federation for Laboratory Medicine (ECLM).This statement, together with the more extensive documents made available on the internet, are a first step towards a European clinical immunology network. The partici-pation of national societies, and the interest

expressed even by those without much in-volvement in clinical immunology at pres-ent, are very encouraging for continuing

actions under the auspices of EFIS.

Concluding remarks

The European image of clinical immunol-ogy has already become clearer through the efforts of EFIS-CIG. Continuing reflections and actions, aided by the growing ease of international communications through the internet, should allow this varied and rich medical discipline to attract more MDs in coming years. A special effort will be made to help provide them with information about clearly defined training programmes,and to try to ensure a comprehensive and consensual immunological education. Con-tinuing cooperation between national groups responsible for training is mandatory if this project is to succeed. It is hoped that the in-teractive window offered by EFIS-CIG will help to harmonize the teaching and practice

of clinical immunology throughout Europe.

We thank members of the Clinical Immunology Group of the European Federation of Immuno-logical Societies (EFIS-CIG) for valuable discus-sions and help in preparing this manuscript. The work of EFIS-CIG is supported by EFIS.

Marie Christine B?n?(bene@grip.u-nancy.fr) is at EFIS-CIG, Laboratoire d?Immunologie, Facult?de M?decine de Nancy, BP 184, 54500 Vandoeuvre les Nancy, France;Hannes Stockinger is at the Institute of Immunology, University of Vienna,Brunner Strasse 59, A-1235 Vienna, Austria;Peter Capel is at the Dept of Immunology, AZU G04 614 Heidelberglaan, 1003584 CX Utrecht,The Netherlands; Helen Chapel is at the Dept of Immunology, John Radcliffe Hospital, Headington,Oxford, UK OX3 9DU; Walter Knapp is at the Institute of Immunology, University of Vienna,Borschkegasse 8a, A-1090 Vienna, Austria.

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Clinical immunology: a unified vision for Europe

Marie Christine Béné, Hannes Stockinger, Peter J.A. Capel, Helen Chapel

and Walter Knapp

s noted by F. Scott Fitzgerald,there are no second acts in American lives. The same cannot be said of drugs; a

better understanding of how a drug works can lead to novel applications. Thalidomide is one example. Approved for use in leprosy,thalidomide is finding uses in immuno-modulation (suppressing graft-versus-host disease) based on its antagonism of tumour necrosis factor, and in cancer therapy based

on its inhibition of angiogenesis.

Growth hormone is a cytokine Growth hormone and its receptor are pro-duced by many cells in the body including haematopoietic and lymphoid cells (M. Dardenne, Paris; R. Schultz, Madison,WI; R. Kooijman, Utrecht; D. Weigent, Birmingham, AL). The regulation of expres-sion of these genes and the pattern of ex-pression in particular cell subsets is unknown.Growth hormone effects are also diverse.The major effects are to increase bone growth,increase lean body mass, decrease fat, de-crease glucose uptake and promote protein synthesis.

Growth hormone receptor is a member of the haematopoietin/cytokine receptor fam-ily. Although it lacks intrinsic kinase activity,the receptor induces tyrosine phosphorylation by signalling through a Janus family kinase

(JAK2) and activating signal transducer and activator of transcription proteins (STAT1, 3and 5). The known steps in cell activation by growth hormone differ subtly , if at all, from the

effects of other cytokines on their receptors.Growth hormone in

haematopoiesis and lymphopoiesis In addition to growth defects, the SnellDBagg dwarf mouse (abnormal anterior pitui-tary function) has profound defects in T-cell immunity, many of which can be reversed

by growth hormone (Ref. 1; W.J. Murphy).However, T- and B-cell numbers, distribu-tion and function appear completely normal in growth hormone-, prolactin- or insulin-like growth factor I (IGF-I)-knockout mice

(Ref. 2; K. Dorschkind, Los Angeles, CA). No obligate role for growth hormone, pro-lactin or IGF-I in lymphoid or myeloid cell development has been noted.

How can these contradictory results be reconciled? Dwarf mice are infertile. There-fore, they emerge as a homozygous fraction of offspring of two heterozygous parents and 75% of the siblings are normal. Immune function and thymic size were normal in dwarf mice raised together with other dwarf mice in the absence of phenotypically nor-mal siblings (Murphy). Thus, the presence of larger normal siblings might be stressing the dwarf mice that develop immune defects;growth hormone might play a homeostatic role in assuring adequate lymphoid and haematopoietic cell generation during times

of stress.

Growth hormone as a thymopoietic factor

Two pathways generate more T cells: the dominant pathway in adults is the expan-sion of post-thymic T cells; the dominant pathway in infancy and childhood is the generation of new T cells from the thymus (Ref. 3; R. Gress, Bethesda, MD). When pe-ripheral T cells expand, memory phenotype cells (usually CD45R0?) expand and the T-cell receptor (TCR) repertoire reflects

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Growth hormone as an immunomodulating

therapeutic agent

William J. Murphy and Dan L. Longo

References

1Joint Committee for Immunology of the Royal College of Physicians and the Royal College of Pathologists, UK. (1994) The role of immunologists and allergologists within the NHS (National Health Service).International Union of Immunological Societies 2Lambert, P .H. et al.(1993) Clinical immunology: guidelines for its

organization, training and certification.Clin. Immunol. Immunopathol.69, 234D2433Fahey , J. (1995) Clinical immunology: a distinct area of immunology.Immunologist 3, 104D1074Bloch, K.J. et al . (1991) Diagnostic laboratory immunology: a subspecialty that encompasses clinical as well as laboratory immunology . J. Allergy Clin. Immunol.88,961D963

5Penny, R. et al . (1986) Clinical immunology in Australia . Immunol. Today 7, 3D4

6Strober, W. (1990) Certification in diagnostic laboratory immunology . J. Allergy Clin.Immunol.85, 816D817

*The Serono Symposium on Growth Hormone in Bone Marrow Transplantation and Immune Deficiency was held in St Petersburg, Florida, USA, on 9D11 October 1999.