On specific T-cell factors

same MBP region. Three years later, when the database was much larger, M,J. Weise and P.R. Carnegie8 found other homologies with this MBP region and viral proteins, i.e. the human T-cell leukemia virus II (HTLV II) gag polyprotein, the baboon endogenous gag polyprotein, the herpes simplex virus glycoprotein E and the hypothetical adenovirus 2 protein F-215 (Ref. 8). During our search, we also found a small homology with the L protein of measles virus (strain udem) (346364) 9. A T-ceil response to minor viral proteins, like P3 A, may be important in a protective immune response. For example, it has been shown that cytotoxic T cells (CTL) that recognize the immediate early protein of murine cytomegalovirus protect mice from lethal infection with this virus. Similarly CTL that recognize the reverse transcriptase and gag proteins of the human immuno-

N. et al. (1990) Science 248, 1016-1019 3 Pearson,W. and Lipman, D. (1988) Proc. Natl Acad. Sci. USA 85, 2444-2448 4 Devereux,J., Haeberli, P. and Smithies, O. (1984) Nucleic Acids Res. 12, 387-395 5 Linberg,A., Stalhandske,P. and Pettersson, U. (1987) Virology 156, 50-63 6 Jenkins, O., Booth, J., Miner, P. et al. (1987)J. Gen. Virol. 68, 1835-1848 7 Jahnke, U., Fisher, E. and Alvord, E. (1985) Science 229, 282-284 Dept of Biochemistry and 8 Weise,M.J. and Carnegie, P. (1988) Microbiology, St Andrews J. Neurochem. 51, 1267-1273 University, St Andrews, 9 Blumberg,B., Crowley,J., Fife KY16 9AL, UK. Silverman,J. et al. (1988) Virology 164, 487-497 The WellcomeTrust and the Multiple 10 Randall, R. and Souberbielle,B. Sclerosis Society provided support for (1990) in Control of Virus Diseases B.E. Souberbielle. (Dimmock,N.J. et al., eds), Cambridge UniversityPress References 11 Grist, N.R., Bell, E.J. and Assaeed, 10ta, K., Matsui, M., Milford, E. et F. (1978) Prog. Med. Virol. 24, al. (1990) Nature 346, 183-187 114-124 2 Wucherpfennig,K., Ota, K., Endo,

deficiency virus have been described (see Ref. 10 for a review). The aetiopathological relevance of the homologies between MBP and viral proteins reported here remains to be tested, although it is interesting that neurological diseases can be caused by Coxsackie viruses 11. This may complement the observations on MS patients described in the review article. Bernard E. Souberbielle Graham Kemp William C. Russell

On specific T-cell factors

Takemori and Tada observed about 90% antigen-specific suppression of IgG responses. I would like to Immunology is in a strange, schizophrenic state concerning some suggest that the reproducibility or simple questions that can readily be otherwise of their basic experiment settled experimentally. There have can reasonably be taken as an acid been many reports of specific T-cell test for the existence of specific T-cell factors but skepticism concerning factors. The experiment requires no the existence of these molecules special reagents or advanced techpersists. For example, Melchers1 niques, and should be readily reprorecently wrote that "... soluble fac- ducible with minimal expenditure of tors [are] antigen-unspecific stimu- time and effort by immunologists lators of antigen-specific responses" interested in knowing for themselves (Melchers' emphasis). Similarly, in a whether specific T-cell factors exist. Various immunologists make recent article on network theory, Varela and Coutinho 2 wrote that various demands concerning more "... V regions exist as cell-bound proof that they would like to see for lymphocyte receptors and as soluble the existence of specific T-cell facimmunoglobulin molecules". Specific tors. But the absence of whatever T-cell factors, if they exist, must additional proof they might demand have V regions, and any reference to is not proof of the nonexistence of them is conspicuous by its absence, the factors. The nonexistence of the especially in a network theory con- factors can be inferred only from text, where they have been ascribed a experiments in which immunologists fail to reproduce the basic central role 3,4. The most extensive and compel- findings. Specific T-cell factors play a key ling experimental evidence supporting the existence of specific T-cell role in a network theory of regulation that my colleagues and I have factors is for specific suppressor factors. An early, prototypical sup- developed3,4. The central problem of pressor T-cell factor experiment was theoretical immunology is to explain published in 1975 by Takemori and how T celts regulate B-cell responses. Tada s. The experiment included Our model explains in simple terms criss-cross specificity controls, and how specific T-cell factors can lead Immunology Today

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to the observed helper and suppressor effects of T cells On B-cell immune responses. It accounts for the switch from IgM to IgG6. It also provides a basis for understanding a considerable amount of other regulatory phenomenology, including the roles of some nonspecific lymphokines, low-zone and high-zone tolerance, MHC restriction and the facts that helper T cells are CD4-bearing T cells while CD8 helper T cells are suppressor T cells. On the other hand, if the factors do not exist, this network theory is wrong. The theory has recently led to the formulation of a model of AIDS pathogenesis7. Geoffrey W. Hoffmann Depts of Microbiology and Physics, University of British Columbia, Vancouver, BC, Canada, V6T 1Z3.

References 1 Melchers, F. (1991) in Basel Institute for Immunology Annual Report, 1990, (Steinberg, C., ed.), p. 9, Basel Institute for Immunology 2 Varela, F. and Coutinho, A. (1991) Immunol. Today 12, 159-166 3 Hoffmann, G.W. (1978) in Theoretical Immunology (Bell, G.I., Perelson, A.S. and Pimbley,G.H., eds), pp. 571-602, Marcel Dekker

rot 12 No. 12 1991

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iiiii i

ed.), pp. 291-319, AddisonWesley 5 Takemori, T. and Tada, T. (1975) J. Exp. Med. 142, 1241-1253 6 Gunther, N. and Hoffmann, G.W.

(1982) J. Theor. Biol. 94, 815-855 7 Hoffmann, G.W., Kion, T.A. and Grant, M.D. (1991) Proc. Natl Acad. $ci. USA 88, 3060-3064

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Manual of Laboratory Immunology (2nd edn) by Linda E. Miller, Harry R. Ludke, Julia E. Peacock and Russell H. Tomar, Lea and Febiger, 1991. £25.25 (xiv + 427pages) ISBN 0 8121 1319 5 Writing practical books is not easy. Just how much should be included? Should the theory behind the experimental method be given ? Should the book be a primary source including all details down to how to" make up the buffers or simply quote published papers? As we all know, methods in papers rarely give enough detail to allow even the initiated to carry out a technique and perhaps this is where the practical book comes into its own in being able to pursue the technique for its own sake. The authors of Manual of Laboratory Immunology have chosen to include rather a large amount of theory in a block at the beginning of the book and also relatively large amounts alongside each technique. The book is really more useful for those who wish to learn about why tests are used and how they are performed than for the active research worker. The title of the book is a misnomer; Manual of "Routine Clinical" Laboratory Immunology would better describe the contents. For this it is excellent, with most of the topics arranged by application, such as 'Infectious disease serology' and 'Autoimmunity', rather than by immunological principle, making it an ideal book for the postgraduate physician trying to get to grips with immunopathology. This is not the book for the young PhD student wanting to use immunological techniques. Basic methods such as how to prepare IgG are not included; monoclonal antibodies are described but the technique is omitted; mouse immunology, the staple diet of the

average immunologist, is completely missing. References after 1988 are rare. The layout is not very helpful for work in the laboratory as the same format is used for theory and practical methods, making it difficult to follow while working at the bench. The methods frequently use manufactured kits. There really seems little point in detailing the package insert as a technique in the book. Most materials are expected to be bought in - looking up the main entry for Ouchterlony technique, one is given the name of a manufacturer from whom to buy ready-made plates! Unfortunately addresses are not given as well, so this is not much help. Reliance on suppliers in the USA without giving either addresses or international suppliers makes the book less useful outside the USA.

This reliance on commercial material saves time but can lead to problems. Perhaps the authors' heparinized tubes always come with preservative-free heparin, but it would be helpful to provide a warning to the many who would find that their standard tubes do contain preservative - which would not help in performing successful lymphocyte function tests. In summary, the background material is informative, but unless one has ready access to the American market and is prepared to buy the author's selection for each test (alternatives are not usually suggested) this text will not provide the ideal recipe book. Frank C. Hay Dept of Cellular and Molecular Sciences, St George's Hospital Medical School, London SW17 ORE, UK.

Hematopoietic Growth Factors in Clinical Applications

ment of patients with a wide range of hematological, malignant, genetic and infectious diseases. The first section deals with the biology of the hematopoietic growth factors. Five chapters review the complex interacting networks of cytokines-in modulating hematopoiesis, the effects of the individual specific growth factors on regulating cell function, the control of production of the various hematopoietic growth factors and the molecular biology of these factors and their specific receptors. The way in which these factors are responsible for the proliferation and maturation of bone marrow stem and progenitor cells to differentiated end cells is described. The cloning of both the genes and receptors for these molecules provides a background for future studies of the three-dimensional structure of these proteins and the molecular regions binding to their respective receptors. The second section deals with transgenic mouse models and

edited by Roland Mertelsmann and Friedhelm Herrmann, Marcel Dekker, 1990. $99.75 USA and Canada/ $119.50 all other countries (xiv + 496 pages) ISBN 0 8247 8203 8 Despite the fact that hematopoietic growth factors have now been investigated for two decades, it is only in the last few years that advances in the manipulation and expression of recombinant genes have made these factors available to clinicians in sufficient quantities for them to be tested clinically. Hematopoietic Growth Factors in Clinical Applications brings together the basic background cellular and molecular biology of these factors and the rapidly widening arena of their clinical application. This is clearly a fast advancing field which is literally rewriting the approach to the manage-

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vol 12 No. 12 1991