Immunology Today, voL 7, No. 9, 1986
Offsetdrukkerij KantersB.V., Alblasserdam. 8 van Vliet, E., Melis, M. and van Ewijk, W. (in press) 9 Huiskamp, R. and van Ewijk, W. J. Immunol. (in press) 10 Inamura, M. Matsuyama,T., Toh, K. etal. (1971) J. NatlCancerlnst. 47, 289-300 11 Santisteran,G.A., Riley,V. and Fitzmaurice, M.A. (1972)Proc. Soc. Exp. BioL Med., 139, 202-206
Contrasuppressor cells in mucosal immunity Sir, In their stimulating review of murine contrasuppressor T (TJ cells Immunol. Today, 1986, 7, 81-86), Green and Ptak emphasized the role of contrasuppression in the mucosal immune system. In particular, they proposed that prevention of hypersensitivity to dietary antigens reflects the concomitant induction of systemic immune tolerance and the restriction of antigen uptake from the gut, and that this is regulated by a local population of Tcs within the gut associated lymphoid tissues (GALT). While we agree that it is important to prevent systemic food hypersensitivity, we believe that the authors' arguments rely on certain assumptions about immune exclusion and oral tolerance to dietary antigens which have not yet been established beyond doubt. First, in mice fed ovalbumin (OVa,), Stokes et al. have shown that immune exclusion by the gut is a r,~.latively unusual occurrence and is highly strain dependent 1. Furthermore, the idea that a secretory antibody response and systemic tolerance are induced in parallel by oral immunization 2 has been challenged by recent studies which showed that local IgA production and systemic tolerance in mice fed keyhole limpet haemocyanin (KLH) did not occur simultaneously3. In contrast, the Ioc-
.letter$12 Kendall, M.D.J. Anat. (in press) 13 van Vliet, E., Jenkinson, E.J., Kingston, R. et al. Eur. J. Immunol. (in press) 14 Nezelof, Ch. (1986)in The Human Thymus. Histophysiology and Pathology (Muller-Hermelink, H.K. ed.) Curr. Top. PathoL 75, Springer-Verlag, Berlin 15 Hall, N.R., McGillis,J.P., Spanelo, B. et aL (1982) in Current Concepts in Human Immunology and Cancer Immunomodulation (Serrou, B. et al. eds.) Elsevier,Amsterdam
16 Kendall, M.D. in Surg~ry of the Thymus (Givel,J.-C. ed.) Springer-Verlag, Berlin 17 Rebar,R.W., Miyake, A., Low, T.L.K. et al. (1981 ) Science 214, 669-671 18 Pierpaoli,W. and Sorkin, E. (1967) Nature (London) 215, 834-837 19 Tatal, N. (1983)in TLymphocytes Today (Inglis,J.R. ed.) Elsevier, Amsterdam 20 Oldstone, M.B.A., Sinha,Y.N., Blount, P. et al. (1982) Science 218, 1125-1127
al and systemic immune responses behaved identically under these conditions, and the authors suggested that suppressor T cells were active in the GALT. The hypothesis that suppressor cells in the Peyer's patch (PP) can prevent a local IgA response has been confirmed using sheep red blood cells (SRBC) as an antigen 4. With respect to the presence of Tcs in the GALT, there are few reports of direct examination of mucosal contrasuppression. Thus, in their original study, Green and his co-workers used in-vitro techniques to show that the normal PP contained a population of cells which had some of the characteristics of Tcs inducers, and did not examine the effect of oral immunization on these cellss. The report by Domen and Mattingly cited in this review suggests that antigen-specific Tcs cells are present in the patch after feeding: however, more information is required on this, and we await publication of the results in full. Although a recent report has suggested that a population of Tcs is responsible for the absence of oral tolerance in SRBC fed C3H/HeJ mice6, it would be incautious to interpret these findings as support for the relevance of T~s to mucosal immunity in general. The T~s described by Suzuki et aL were isolated from the spleen rather than the GALT, they were induced after prolonged feeding of LPS-unresponsive C3H/ HeJ mice, and were not present in normal, congenic C3H mice. In addition, we believe that feeding SRBC to
mutant mice may not be an ideal system to study regulation of immunity to dietary antigens, as our own findings indicate that the protein antigen OVA and SRBC have very different effects after oral administration to both normal and LPS-unresponsive mice7. It is likely that immune responses to dietary protein antigens are more relevant to the clinical situation. Therefore, we suggest that detailed studies of mucosal Tcs activity in animals fed proteins are required to prove an essential role for this intriguing population of cells in preventing food hypersensitivity.
Alan G. Lamont Allan Mcl. Mowat UniversityDepartment of Bacteriologyand Immunology, Western Infirmary, Glasgow G116NT, UK
References 1 Stokes,C.R. Swarbrick, E.T.and Soothill, J.F.(1983) C/in. Exp./mmuno/. 52,678-684 2 Challacombe,S.J.and Tomasi,T.B. (1980) J. Exp. Med. 152, 1459-1472 3 Elson,C.O. and Ealding, W. (1984) J. Immunol. 133, 2892-2897 4 MacDonald, T.T. (1983) Eur. J. Immunol. 13, 138-142 5 Green, D.R., Gold, J., St. Martin, S. et al. (1982) Proc. NatlAcad. Sci. USA 79, 889-892 6 Suzuki, I., Kiyono, H., Kitamura, K. et al. (1986) Nature (London) 320, 451454 7 Mowat, A.McI., Thomas, M.J.,. MacKenzie, S. et al. Immunology (in press)
255
Offsetdrukkerij KantersB.V., Alblasserdam. 8 van Vliet, E., Melis, M. and van Ewijk, W. (in press) 9 Huiskamp, R. and van Ewijk, W. J. Immunol. (in press) 10 Inamura, M. Matsuyama,T., Toh, K. etal. (1971) J. NatlCancerlnst. 47, 289-300 11 Santisteran,G.A., Riley,V. and Fitzmaurice, M.A. (1972)Proc. Soc. Exp. BioL Med., 139, 202-206
Contrasuppressor cells in mucosal immunity Sir, In their stimulating review of murine contrasuppressor T (TJ cells Immunol. Today, 1986, 7, 81-86), Green and Ptak emphasized the role of contrasuppression in the mucosal immune system. In particular, they proposed that prevention of hypersensitivity to dietary antigens reflects the concomitant induction of systemic immune tolerance and the restriction of antigen uptake from the gut, and that this is regulated by a local population of Tcs within the gut associated lymphoid tissues (GALT). While we agree that it is important to prevent systemic food hypersensitivity, we believe that the authors' arguments rely on certain assumptions about immune exclusion and oral tolerance to dietary antigens which have not yet been established beyond doubt. First, in mice fed ovalbumin (OVa,), Stokes et al. have shown that immune exclusion by the gut is a r,~.latively unusual occurrence and is highly strain dependent 1. Furthermore, the idea that a secretory antibody response and systemic tolerance are induced in parallel by oral immunization 2 has been challenged by recent studies which showed that local IgA production and systemic tolerance in mice fed keyhole limpet haemocyanin (KLH) did not occur simultaneously3. In contrast, the Ioc-
.letter$12 Kendall, M.D.J. Anat. (in press) 13 van Vliet, E., Jenkinson, E.J., Kingston, R. et al. Eur. J. Immunol. (in press) 14 Nezelof, Ch. (1986)in The Human Thymus. Histophysiology and Pathology (Muller-Hermelink, H.K. ed.) Curr. Top. PathoL 75, Springer-Verlag, Berlin 15 Hall, N.R., McGillis,J.P., Spanelo, B. et aL (1982) in Current Concepts in Human Immunology and Cancer Immunomodulation (Serrou, B. et al. eds.) Elsevier,Amsterdam
16 Kendall, M.D. in Surg~ry of the Thymus (Givel,J.-C. ed.) Springer-Verlag, Berlin 17 Rebar,R.W., Miyake, A., Low, T.L.K. et al. (1981 ) Science 214, 669-671 18 Pierpaoli,W. and Sorkin, E. (1967) Nature (London) 215, 834-837 19 Tatal, N. (1983)in TLymphocytes Today (Inglis,J.R. ed.) Elsevier, Amsterdam 20 Oldstone, M.B.A., Sinha,Y.N., Blount, P. et al. (1982) Science 218, 1125-1127
al and systemic immune responses behaved identically under these conditions, and the authors suggested that suppressor T cells were active in the GALT. The hypothesis that suppressor cells in the Peyer's patch (PP) can prevent a local IgA response has been confirmed using sheep red blood cells (SRBC) as an antigen 4. With respect to the presence of Tcs in the GALT, there are few reports of direct examination of mucosal contrasuppression. Thus, in their original study, Green and his co-workers used in-vitro techniques to show that the normal PP contained a population of cells which had some of the characteristics of Tcs inducers, and did not examine the effect of oral immunization on these cellss. The report by Domen and Mattingly cited in this review suggests that antigen-specific Tcs cells are present in the patch after feeding: however, more information is required on this, and we await publication of the results in full. Although a recent report has suggested that a population of Tcs is responsible for the absence of oral tolerance in SRBC fed C3H/HeJ mice6, it would be incautious to interpret these findings as support for the relevance of T~s to mucosal immunity in general. The T~s described by Suzuki et aL were isolated from the spleen rather than the GALT, they were induced after prolonged feeding of LPS-unresponsive C3H/ HeJ mice, and were not present in normal, congenic C3H mice. In addition, we believe that feeding SRBC to
mutant mice may not be an ideal system to study regulation of immunity to dietary antigens, as our own findings indicate that the protein antigen OVA and SRBC have very different effects after oral administration to both normal and LPS-unresponsive mice7. It is likely that immune responses to dietary protein antigens are more relevant to the clinical situation. Therefore, we suggest that detailed studies of mucosal Tcs activity in animals fed proteins are required to prove an essential role for this intriguing population of cells in preventing food hypersensitivity.
Alan G. Lamont Allan Mcl. Mowat UniversityDepartment of Bacteriologyand Immunology, Western Infirmary, Glasgow G116NT, UK
References 1 Stokes,C.R. Swarbrick, E.T.and Soothill, J.F.(1983) C/in. Exp./mmuno/. 52,678-684 2 Challacombe,S.J.and Tomasi,T.B. (1980) J. Exp. Med. 152, 1459-1472 3 Elson,C.O. and Ealding, W. (1984) J. Immunol. 133, 2892-2897 4 MacDonald, T.T. (1983) Eur. J. Immunol. 13, 138-142 5 Green, D.R., Gold, J., St. Martin, S. et al. (1982) Proc. NatlAcad. Sci. USA 79, 889-892 6 Suzuki, I., Kiyono, H., Kitamura, K. et al. (1986) Nature (London) 320, 451454 7 Mowat, A.McI., Thomas, M.J.,. MacKenzie, S. et al. Immunology (in press)
255
