161
Immunology Today, vol. 5, No. 6, 1984
Suppressor cells in immunological maturation SIR, In
a
very
interesting
discussion
(Immunol. Today 1984, Vol. 5, 34-36)
Bertie Argyris suggested that immunological immaturity at birth is a consequence of high suppressor cell activity. After suppressor cells had been discovered simultaneously and independently in different laboratories 1,2, it was soon realized that suppressor cell activity is strong in the late embryonic and early post-natal thymus, and declines subsequently >6. In an analogy to observations cited by Argyris, these studies revealed an inverse correlation between the level of suppressor-cell activity and another immunological function, i.e. graft-v.-host reactivity 5. They revealed also that suppressor activity is 'intrinsic', i.e. present in animals without experimental antigenic stimulation 2-5. These studies also suggested that strong embryonic and early post-natal suppressor-cell activity may play an important role in the generation of self tolerance 3-5. Miller and colleagues showed that the antigen specificity of certain types of suppressor cell is determined by antigenic determinants on the surface of these cells 7's. This principle seems to apply to
suppressor cell systems described in several other laboratories 9-n. In each case, the suppressor cells inhibit immune responses against antigenic determinants which are either integral parts of the suppressor cell m e m b r a n e 7 ,0 or otherwise attached to the suppressor cell surface 7'11. Miller has pointed out that suppressor cells of this type, he has proposed to term them 'veto' cells might be important in the generation of self tolerance; remarkable that veto cells have been observed a m o n g very different cell classes, including Thy 1- cells 8 and T cells of the Lyt 2- (Ref. 10) and Lyt 2 + variety 9'1°. In most instances, they were irradiation sensitive 8-1°. These observations suggest that 'veto' suppression might be mediated by cells of different lineages which simply have in common the functional effect of delivering a non-spec!fic suppressor signal to an antigen-specific subset o f T or B lymphocytes. This signal could be a simple toxic substance of low moleculer weight and with a short range of action. Obviously, antigen-specific suppression of the 'veto' type would not require a highly specialized suppressor cell with a sophisticated antigen-specific product. Perinatal thymic suppressor cells, like 'veto' cells, also most effectively suppressed i m m u n e responses against antigens expressed on their own surface 5. They were strongly radiation-sensitive 5
and did not require previous stimulation by antigen in order to mediate suppression. Although there is no direct proof for it, there is much sense in the suggestion that suppressor cells of the 'veto' type are particularly abundant in the perinatal period and are responsible for the immunological immaturity at birth and to a large extent also for the induction of self-tolerance. WULF DR()GE Institut fur Immunologic und Genetik, Deutsches Krebsforschungszentrum, I M Neuenheimer Feld 280, D 6900 Heidelburg, FRG.
References 1 Gershon, R. K. andKondo, K. (1971)Nature (London) 234, 549-551 2 Dr6ge, W. (1971) Nature (London) 234, 549-551 3 DrSge, W. (I973) Eur. J. Immunol. 3, 804-8 t 1 4 DrSge, W. (1975) Proc. Natl Acad. Sci. 72, 2371-2374 5 DrSge, W. (1976) Eur. J. bnmunol. 6, 279-287 6 DrSge,W. and Zucker, R. (1975) Transplant. Rev. 25, 3-35 7 Miller, R. G. (1980) Nature (London) 287, 544-546 8 Muraoka, S. and Miller, R. G. (1980)J. Exp. Med. 152, 54-71 9 Rammensee, H.-G., Nagy, Z. A. and Klein, J. (1982) Eur. J. Immunol. 12, 930 934 10 Fink, P. J., Weissman, I. L. and Bevan, M. J. (1983)j~ Exp. Med. 157, 141-154 ll Moorhead, J. W. and Scott, D. W. (1977) Cell. ImmunoL 28, 443-448
Immunology Today, vol. 5, No. 6, 1984
Suppressor cells in immunological maturation SIR, In
a
very
interesting
discussion
(Immunol. Today 1984, Vol. 5, 34-36)
Bertie Argyris suggested that immunological immaturity at birth is a consequence of high suppressor cell activity. After suppressor cells had been discovered simultaneously and independently in different laboratories 1,2, it was soon realized that suppressor cell activity is strong in the late embryonic and early post-natal thymus, and declines subsequently >6. In an analogy to observations cited by Argyris, these studies revealed an inverse correlation between the level of suppressor-cell activity and another immunological function, i.e. graft-v.-host reactivity 5. They revealed also that suppressor activity is 'intrinsic', i.e. present in animals without experimental antigenic stimulation 2-5. These studies also suggested that strong embryonic and early post-natal suppressor-cell activity may play an important role in the generation of self tolerance 3-5. Miller and colleagues showed that the antigen specificity of certain types of suppressor cell is determined by antigenic determinants on the surface of these cells 7's. This principle seems to apply to
suppressor cell systems described in several other laboratories 9-n. In each case, the suppressor cells inhibit immune responses against antigenic determinants which are either integral parts of the suppressor cell m e m b r a n e 7 ,0 or otherwise attached to the suppressor cell surface 7'11. Miller has pointed out that suppressor cells of this type, he has proposed to term them 'veto' cells might be important in the generation of self tolerance; remarkable that veto cells have been observed a m o n g very different cell classes, including Thy 1- cells 8 and T cells of the Lyt 2- (Ref. 10) and Lyt 2 + variety 9'1°. In most instances, they were irradiation sensitive 8-1°. These observations suggest that 'veto' suppression might be mediated by cells of different lineages which simply have in common the functional effect of delivering a non-spec!fic suppressor signal to an antigen-specific subset o f T or B lymphocytes. This signal could be a simple toxic substance of low moleculer weight and with a short range of action. Obviously, antigen-specific suppression of the 'veto' type would not require a highly specialized suppressor cell with a sophisticated antigen-specific product. Perinatal thymic suppressor cells, like 'veto' cells, also most effectively suppressed i m m u n e responses against antigens expressed on their own surface 5. They were strongly radiation-sensitive 5
and did not require previous stimulation by antigen in order to mediate suppression. Although there is no direct proof for it, there is much sense in the suggestion that suppressor cells of the 'veto' type are particularly abundant in the perinatal period and are responsible for the immunological immaturity at birth and to a large extent also for the induction of self-tolerance. WULF DR()GE Institut fur Immunologic und Genetik, Deutsches Krebsforschungszentrum, I M Neuenheimer Feld 280, D 6900 Heidelburg, FRG.
References 1 Gershon, R. K. andKondo, K. (1971)Nature (London) 234, 549-551 2 Dr6ge, W. (1971) Nature (London) 234, 549-551 3 DrSge, W. (I973) Eur. J. Immunol. 3, 804-8 t 1 4 DrSge, W. (1975) Proc. Natl Acad. Sci. 72, 2371-2374 5 DrSge, W. (1976) Eur. J. bnmunol. 6, 279-287 6 DrSge,W. and Zucker, R. (1975) Transplant. Rev. 25, 3-35 7 Miller, R. G. (1980) Nature (London) 287, 544-546 8 Muraoka, S. and Miller, R. G. (1980)J. Exp. Med. 152, 54-71 9 Rammensee, H.-G., Nagy, Z. A. and Klein, J. (1982) Eur. J. Immunol. 12, 930 934 10 Fink, P. J., Weissman, I. L. and Bevan, M. J. (1983)j~ Exp. Med. 157, 141-154 ll Moorhead, J. W. and Scott, D. W. (1977) Cell. ImmunoL 28, 443-448
