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immunology to@, December 1980

scavenger when given orally the authors suggest the possibility of in-vivo enhancement of neutrophil function. Vitamin E is another example of an agent functioning as an auto-oxidant. In the manipulation of the oxygen radicals generated by phagocytozing cells it must, however, be remembered that the radicals are necessary for killing off many common pathogens. An ideal agent in clinical practice for moderation of the consequences of oxygen radical production should protect phagocyte cell membranes as well as surrounding cells, without interfering with radical production and release into the phagocytic vacuoles that are part of the normal microbial killing process. B E N G T BJORKS'I'EN

D@artment of Biological Research, Pharmacia AB, Uppsala, Sweden

References 1 Spielberg, S. P., Boxer, L. A., Oliver, J. M., Allen, J. M. and Schulman,J. D. (1979) Br.J. Haemalol. 42,215-223

2 Roos, D., Weening,R. S., Voetman, A. A., van Schaik, M. L.J., Bot, A. A. M., Meerhof, L. J. and Loos, J. A. (1979) Blood 53, 851-866 3 Roos, D., Weening, R. S., Wyss, S. R. and Aebi, H. E. (1980)J. Clin. Invest. 65, 1515-1522 4 Althaus, D., Keller, H. V., Hess, M. W. and Cottier, H. (1980) Int. Arch. Allergy AppL Immunol. 61,321-328 5 Strauss, R. B., Snyder, E. L., Wallace, P. D. and Rosenberger, T. G. (1980)J. Lab. Clin. Med. 95,897-904 6 Ferrante, A., Beard, L. J. and Thong, Y. H. (1979) Clim Exp. Immunol. 39, 532-537 7 Boxer, L. A., Allen, J. M. and Baehner, R. L. (1978)J. Lab. Clin. Med. 92, 730-736

Circulating immune complexes in infectious tropical diseases Normal hosts respond to the introduction of heterologous antigens with the synthesis of specific antibodies and the consequent formation of circulating i m m u n e complexes (CIC) which aid antigen clearance. CIC are a component of normal i m m u n e responses, but they sometimes assume a r61e in tissue damage. This may happen either because of the intrinsic characteristics of the infecting organism a n d / o r because of the nature of the host immune response. CIC may remain in circulation and, through complement activation, trigger pathogenic effects in sites such as kidney, joints, skin, and central nervous system. Until recently CIC could be detected only after deposition in the tissues, but now several methods are available for the identification of CIC j. The study of the dynamics of the appearance and disappearance of CIC during infectious and parasitic disease may permit the reconstruction of the natural history of the disease concerned. Tropical infectious diseases are of particular interest for several reasons: some tropical infectious and parasitic organisms act as polyclonat activators of B cells2~3;the symptoms of some of these diseases resemble those of serum sickness, the classical immunecomplex-mediated disorder; humoral i m m u n i t y has no protective role in many tropical infectious diseases. Evidence for the presence of CIC in such diseases has been reported in several recent papers. In d e n g u e haemorragic fever Ruangjjrachudorn el a[. 4 not only detected CIC but also established a correlation between CIC levels and clinical severity. In leprosy, the now universally accepted Ridley-Joplings classification divides the disease into five forms ranging from tuberculoid to lepromatous; in the tuberculoid form the highest level of cell-mediated i m m u n i t y and the lowest levels of Mycobacterium leprae are found, while the lepromatous form is characterised by the lowest levels of cell-mediated i m m u n i t y and the high© Elsevier~North-Holland BiomedicalPress 1980

est levels of mycobacteria, heteroantibodies, and autoantibodies. The hypothesis that levels of CIC in the lepromatous form of leprosy might be higher than in other forms was only partially confirmed by a W.H.O. collaborative study 6 in which only 3 out of 18 methods for detecting CIC were able to discriminate between the two forms of leprosy. In a study conducted in this laboratory 7, such a discrimination was also impossible. In the serum of one patient with kala-azar (leishmaniasis), Casali and Lamberff were able to detect high levels of CIC and to characterize them by identifying anti-leishmania antibody and a n t M g G antibody activity in the complexes. High levels of CIC have also been found in african trypanosomiasis in the blood and in the cerebrospinal fluid (CSF), mostly in the patients with definite involvement of the central nervous system 9. The same patients also had very high levels of serum and CSF Ig and high levels of rheumatoid-factor-like anti-immunoglobulin antibodies, all signs of the polyclonal activation probably responsible for the presence of the complexes. The question of CIC levels in malaria has been recently reviewed ~° with the conclusion that in malaria CIC occur but are rapidly cleared, so that there is a speedy resolution of abnormalities such as glomerulonephritis, cerebral malaria, or anemia. In the acute form of schistosomiasis, which has certain features in common with serum sickness, CIC levels are sometimes high, in contrast with the low levels found in the chronic form jl. CIC probably related to the clinical symptomatology were also found in six patients with trichinosis 12 and in some of 14 subjects with filariasis ('. Paganelli el a]. 13 detected high CIC levels in oncocerchiasis and were able to correlate the CIC levels with the clinical severity of the disease. One can conclude from this accumulation of data

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that in the majority of infectious tropical diseases there is convincing evidence that C I C are responsible for some of the s y m p t o m s observed. T h e ability to detect these C I C now provides a n o p p o r t u n i t y to clarify the pathogenesis of these diseases a n d to p l a n a more rational a p p r o a c h to therapy. RAFFAELE

D ~AMELIO

Institute of Internal Medicine 111, l)ivzsion of Infectious Diseases, Policlinieo Umberto 1°, 00161 Rome, Italy.

References I WHO Report of a Scientific Group (1977) WHO Teek. Rep. Series, N 606 2 Greenwood, B. M. (1974), LanceS, i, 435 3 Lous, J. A. and Lambert, P.H. (1979) Springer Semin. Itnmunopalhol. 2, 215-228

4 Ruangjjrachudorn, W, Boonpucknavig, S. and Nimmainitya, S. (1979) Clin. Fxp. lmmunot. 36, 46-54 5 Ridley, D. S. and Jopling, W. H. (1966) Int. J. Lepr. 34, 255-273 6 Lambert, P. H., Dixon, F.J. and Zubler, R. H. et aL (1978) J. Clin. Lab. lmmunol. 1, 1-15 7 Nuti, M., D'Amelio, R., Seminara, R., Palmisano, L. and Muff, F. (1981) Inl. J. Lepr. (in press) 8 Casali, P. and Lambert, P. H. (1979) C/in. Fxp. Itnmunol. 37, 295-309 9 Lambert, P. H., Berney, M. and Kazyumba, G. (1981)J. Clin. lrtvest. (in press) 10 Houba, V., Lambert, P. H., Mackey, L. J. and Miescher, P. A. (1980) SpringerSemin. ImmunopathoL 2, 359-371 11 Lawley, T. J., Ottesen, E. A., Hiatt, R. A. and Gazze, L. A. (1979) CTin.Exp. ImmunoL 37,221-227 12 Geniteau, M., Verroust, P. J. and Smith, M. D. et at. (1977) Clin. Exp. lmmunol. 30, 141-145 13 Paganelli, R., Ngu, J. H. and Levinsky, R.J. (1980) (.'tin. Exp. lmmunoL 39, 570-575

(reuiews T-cell growth factors: interleukin 2 James Watson, Diane Mochizuki and Steven Gillis* Department of Microbiology, University of California, Irvine, California 92717, U.S.A. and *Basic Immunology Program, Fred Hutc~hinson Cancer Center, Seattle, Washington 98104, U.S.A.

One of the key aspects of immunoregulation is the abil@ of T-cell subpopulations to help or suppress the expression of antigen-sensitive lymphocytes. The cloning of lymphoid cells - - usually neoplastic cells - - has long been a basic approach to the analysis of cellular function within the immune system but in the investigation of how Tcells act, T-cell lyrnphoma lines have been of limited value because the antigen specificity of their effector junctions could not be detected. Now, however, lymphokines have been isolated which permit the growth of continuous lines of human and mouse T-cells with known specificity Jbr antigen z-8. In this review, James Watson and his colleagues discuss these lymphokines and some of the outstanding questions about their nature and function. L y m p h o k i n e research in cellular i m m u n o l o g y has been d o m i n a t e d by the search for h u m o r a l factors that replace helper T-ceils in the i n d u c t i o n of h u m o r a l or cell-mediated i n m m n e responses in vitro ')'11. W i t h the development of a n increasing n u m b e r of assays in vitro for l y m p h o k i n e activities in the s u p e r n a t a n t s of antigen-activated or mitogen-activated cultures of m u r i n e , rat, or h u m a n cells, a large n u m b e r of factors were described. T h e absence in most instances, of a clear association between a purified effector molecule a n d a p a r t i c u l a r biological assay has m a d e analysis very difficult. T w o factors that m o d u l a t e the activation of m u r i n e lymphocytes have been distinguished by biochemical a n d biological criteria 12. Because both factors have several biological properties in c o m m o n , i n c l u d i n g the e n h a n c e m e n t of t h y m o c y t e mitogenic

response to p h y t o h a e m a g g l u t i n i n (PHA) a n d conc a n a v a l i n A (con A), a n d b o t h stimulate antigen-dependent, cell-mediated a n d h u m o r a l i m m u n e responses in culture, a definitive assay to distinguish t h e m was sought. T h e ability to stimulate c o n t i n u o u s growth has proved to be this distinguishing property. O n e of these factors, o b t a i n a b l e from h u m a n and mouse macrophages (i.e. a monokine) as well as culture s u p e r n a t a n t s of m a c r o p h a g e tumors, had a tool. wt a r o u n d 15,00013,14. T h i s m o n o k i n e was originally designated lymphocyte-activating factor (LAF) 15. T h e second factor, a m u r i n e spleen-cell product described by C h e n a n d D i S a b a t o I(' as a 30,000-35,000 mot. wt t h y m o c y t e - s t i m u l a t i n g factor (TSF) a n d o b t a i n a b l e from m u r i n e , rat a n d h u m a n sources 16-18, differed from L A F in having the ability to promote © Elsevier/North-Holland Biomedical Piess 1980

Circulating immune complexes in infectious tropical diseases.

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