Immunology Today, vol. 5, No. 8, 1984

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Brain neocortex and the i m m u n e system SIR, I read with the utmost interest the review by Besedovsky et aL (Immunol. Today, Vol. 4, pp. 342-346) on the influence of some parts of the brain, particularly the hypothalamus, on the i m m u n e system as assessed by humoral responses. Neocortical brain structures also seem to influence the i m m u n e system and there is evidence for lateralization (a left/right difference). After a left-sided neocortical lesion, the spleen T-cell n u m b e r is reduced to about half that of normal or sham-operated controls; these cells have impaired or inhibited responses to antigens, alloantigens and T-cell mitogens, compared with an equivalent n u m b e r of control cells 1'2. In contrast, b o t h the percentage of T cells and their responsiveness are increased after destruction of the right brain neocortex ~'4'5'6. A n intact brain neocortex is also essential for normal N K activity5 8 and the expression of T-cell surface antigens is altered by neocortical lesions (G. Renoux, unpublished observations). T h e neocortex seems not to affect B cells or macrophages directly. These findings cannot be attributed to the influence of stress or poor health. Unlike some studies on the role of other regions of the central nervous system (CNS) that were performed within a week post-lesion, ten weeks were allowed to elapse between surgery and testing; mice with a unilateral lesion served as controls for symmetrically lesioned mice, together with sham-operated and no-surgery controls. No spontaneous deaths were recorded during the course of the studies. Hemispheric lateralization for the control of T cell-mediated activities in the mouse is present at a population level, as assays assessed over three years in large groups of mice repeatedly gave similar results. Recruitment and functional activity of cells from the T-cell lineage could therefore be due to a balanced brain assymetry in which the right hemisphere may control the inductive ~nfluence of signals emitted by the left hemisphere6. T h e synthesis of factors active on the T-cell lineage is controlled and regulated by the neocortex 9. C u r r e n t studies also suggest that an anterior pituitary pathway is involved. There are now reports of interactions . between the hypothalamus and i m m u n e

system 10,11,and indications that lymphocyte products influence brain activity 12'13 and brain peptides influence lymphocytes 14,15. Furthermore, a pathway has been traced between hypothalmic neurons a n d the neocortex 16. These data suggest that a cascade of interacting signals from brain neocortex may constitute the efferent arc of a physiological network of i m m u n e regulation. Products of macrophages or activated lymphocytes, such as prostaglandins, interferons, interleukins and catecholamines, may represent the efferent link from the i m m u n e system to the CNS. T h e midbrain seems to represent a relay in which neocortically or immunologically induced modification of neurotransmitter levels would, in turn, modify both behaviour and activity of the i m m u n e system. G. RENOUX Department d 'Immunologie, Faculte de Medeeine, 37032 TOURS-Cedex, France.

References 1 Renoux, G., Bizi~re, K. and Guillaumin, j. M. (1980). C. R. Acad. Sci. 290D, 719

'Mucosal' mast cells SIR, W e read with great interest the review by EllenJarrett and David H a i g entitled: 'Mucosal M a s t Ceils in vivo and in vitro' (Imrnunol. Today, Vol. 5, pp. 115-119). These authors have done a fine job of reviewing this rapidly evolving and complicated field. W e would like to emphasize certain issues raised in this review b u t also interject caution in some of the stated or implied central concepts and hypotheses. As the authors stated i n their first sentence, investigations in the rat have provided most of the information about mast cell subpopulations, although evidence is now available in other species including man. In m a n m u c h current knowledge is based upon histochemical studies, although functional assessments of heterogeneity are now appearing in the literature1'2 W h e t h e r histochemical and functional distinctions are as closely linked in m a n and other animals as in the rat 3 is a n important issue in view of its scientific and therapeutic implications. T h e nomenclature of the so-called 'atypical or mucosal' mast cell has already created, and will continue to create conceptual difficulties. As the reviewers point out in their final sentence, 'atypical' as presently used merely reflects the chronology of discovery and indeed this cell m a y represent the characteristics of the predominant mast cell subpopulation. T h e term 'Mucosal'

2 Bizibre, K., Renoux, G., Renoux, M. et aL (1980) Neurosci. Abst. 6, 31 3 Bizibre, K, Renoux, M. and Renoux, G. (1982) Neuroscience 7, 528 4 Renoux, G., Bizi~re, K., Renoux, M. et aL (1982) Int. J. Immunopharm. 4, 290 5 Renoux, G., Bizibre, K., Renoux, M. et aL (1982) Immunobiology 163, 148 6 Renoux, G., Bizi~re, K., Renoux, M. etal, (1983)J. Neuroimmunol. 5, 227 7 Bardos, P., Degenne, D., Lebranchu, Y. et al. (1981) Scand. J. ImmunoL 13, 609 8 Renoux, G., Bizi~re, K., Bardos, P. et aL (1982) In N K cellsand otherEffector Cells(R. B. Herberman, ed.), pp. 639-643, Academic Press, New York 9 Renoux, G., Bizi~re, K., Renoux, M. et aL (1983) Scand. J. Immunol. 17, 45 10 Cross, R. J., Markesbery, W. R., Brooks, W. H. et al. (1980) Brain Res. 196, 79 11 Roozman, T. L., Cross, R. J., Brooks, W. H. et al. (1982) Immunology 45,737 12 Blalock, J. E. and Smith, E. M. (1981) Biochem. Biophys. Res. Commun. 101,472 13 Oppenheim, J. J. and Gery, I. (1982) ImmunoL Today 3, 13 14 Gilman, S. C., Schwartz, J. M., Milner, R.J. etal. (1982) Proc. NatlAcad. Sci. USA 79, 4226 15 Johnson, H. M., Smith, E. M., Torres, B. et aL (1982) Proc. Natl Acad. Sc£ USA 79, 4171 16 Vincent, S. R., H6kfelt, T., Skirboll, L. R. et aL (1983) Science 220, 1309 despite its current wide usage, is inaccurate because: (a) both mast cell types are present in mucosal tissues, and (b) the histochemically 'atypical' type is found, often as frequently as the 'typical' type, in sites other than the mucosa, e.g., smooth muscle of intestine 4, pulmonary p a r e n c h y m a (Shanahan, MacNiven, Bienenstock and Befus, unpublished) and skin 5. Given existing knowledge, which is restricted both in the diversity of tissues surveyed and in the species studied, it is premature to provide an acceptable nomenclature for mast cell subpopulations based upon functional characteristics or tissue distribution. T o minimize the potential impact of a misleading nomenclature, perhaps arbitrary categories, type I, II etc., would be appropriate. Moreover, these categories would have to be species specific until ontogenetic and functional analogies are firmly established. For example, 'typical' mast cells derived from the mouse peritoneal cavity are functionally distinct from rat peritoneal mast cells in their responsiveness to secretagogues 6, dependence upon phosphotidylserine 6'7 (Befus and Neilson unpublished observations) and responsiveness to anti-allergic compounds (disodium cromoglycate inhibits rat peritoneal mast cell secretion but is inactive against mouse peritoneal mast cells) a. T h e spectrum of such mast cell heterogeneity must be defined. This is not the forum to establish a new nomen" clature. Perhaps such a task can be

Brain neocortex and the immune system.

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