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Autoreactive T cells and graft-versus-host disease
Immunology Today, Vol. 11, No. 4 1990
Comments on syngeneic GVHD Sir, In his shor~ review on 'Graft-versushost disease: an alternative hypothesis' (Immunol. Today, 1989, 10, 362-364), Parkman discussed among other issues some aspects of syngeneic GVHD. The author referred to an article by Glazier and coworkers ~ as the first demonstration of syngeneic GVHD in adult animals. These experiments dealt with Cyclosporin-A-induc,:d GVHD which occurred only after total body irradiation (TBI) that included the thymus, which suqgested that damage to t ~'- thynuc stroma was a ,~'quirement for the devek,..')ment of synqeneic GVHD. Parkman also refers to similar clinical syndromes observed by Cheney and Sprent 2 in neonatally thymectomized and CyclosporinA-treated mice. This review is incomplete, in that it ignores many previous reports on GVHD such as symptomat,~logy in the absence of a bone marrow 9raft of foreign origin. A disease termed isologous secondary disease (iselogous was used for syngeneic and secondary disease was used for what later became known as GVHD) was described more than twenty years earlier in mice surviving high lethal dose T8! and rescue w!th small numbers of syngeneic bone marrow cells 3-s and in mice surviving an LD8o of TBI (Refs 6,7). The histopathological changes in these mice were similar to those of allogeneic GVHD, but generally less severe. Histological analysis of the thymus 8 revealed an ;rreversible decrease in the number of epithelial cells of the thymus and the disease could be prevented by implantation of syngeneic newborn thymus fr3gments after the TBI and bone marrow transplantation 9. These thymus grafts were pre-irradiated to inactivate the T lymphocytes. Just as in the case of Cyclosporin-A-induced syngeneic GVHD, all the evidence pointed to 'thymic stromal damage' as a causative factor. As regards the occurrence of similar syndromes in neonataiiy thymectomized mice, there is exteqsive literature on autoimmunp reactions in these animals, without additional treatment with Cyclosporin A. This so-called post-thyrr~ectomy syndrome was already described in 1964 (Ref.
10) and shortly afterwards confirmed and extended by Monier ~ ~,. More recently it was also reported in thymectomized adult mice subjected to sublethal TBI (Ref. 14). All these original observations are accessible via modern reviews is. The different experimental conditions that were found to provoke syngeneic and autologous GVHD provide interesting opportunities for a re-analysis with the help of modern reagents.
D.W. van Bekkum Radlobiological Institute TNO, PO Box 5815, 2280 HV Rijswijk, The Netherlands.
References 1 Glazier, A., Tutschka, PJ., Farner, E.R. et al. (1983)J. Exp. Med. 158, 1-8 2 Cheney, R.T. and Sprent, J. (1985) Transplant. Proc. 17, 528-530 3 Barnes, D.W.H., Ford, C.E., Ilbery, P.L.T. et al. (1957) J. Cell. Comp. Physiol. 50, 123 4 Van Bekkum, D.W., Vos, O. and Weyzen, W.W.H. (1959)J. Natl Cancer Inst. 23, 75-89 5 Barnes, D.W.H., Loutit, J.F. and Micklem, HS. (1962)in Mechanisms of
Immunological Tolerance (Hasek, M, Lengerova, A. and Vqtlskova, M., eds), p. 371, Publishing House of the Czechoslovak Academy of Sciences 6 Mole, R.H. (1956) Br. J. Racliol. 29, 563-569 7 Corp, M.J. and Neal, F.E. (1959) Int. J. Radiat. Biol. 1,256-265 8 Van Bekkum, D.W. (1967) Brookhaven Symp Biol. 20, 190-211 9 Van Bekkum, D.W. (1969)iq Comparative Cellular and Species Radiosensitivity (Bond, V.P. and Sugahara, T., eds), pp. 175-192, Igaku Shoin 10 De Vries, M.J., Van Putten, L.M., Balner, H. et al. (t964)Rev. Fr Etud. Clin. Biol. 9, 381-397 11 Thivolet, J. and Monier, J.C. (1969) Rev. Ft. Etud. Clin. Biol. 14, 132-143 12 Monier, J.C., Thivolet, J., Sepetjian, M. (1969) Rev. Ft. Etud. Clin. Biol. 14, t85-188 13 Monier, J.C. (1972) Contr61e par ie Thymus et les Cellu~es T, des Phenomenes d'Auto Immunisation et de Competition Antigenique, Ediprim 14 Ansar Ahmed, S. and Penhale, W.J. (1981) Experientia 37, 1341-1343 15 Van Bekkum, D.W. and LSwenberg, B., eds (1985) Bone Marrow Transplantation: Biological Mechanisms and Clinical Practice, Marcel Dekker
Autoreactive T cells and graft-versus-host disease
in NZB mice fits in well with Park!!lan's suggestion of an autgregula"(ion oetect.
R. Parkman (Immunol. Today, 1989, 10, 362-364 and Ref. 1) has drawn attention to the possibility that autoreactive T cells may be partly respon sible for initiating GVH disease, and quotes experiments on syngeneic splenomegaly. This phenomenon was first reported some years earlier 2 and the fact that it was most marked
Department of Imr~unology, University College and MiddlesexSchoolof Medicine,Arthur Stanley House, 40-50 Tottenham Street, London WIP 9PG, UK.
John Playfair
Sir,
Cytotoxic effector mechanisms Sir, In our recent book review of Current Topics in Microbiology and Immunology: Cytotoxic Effector Mechanisms, edited by E.R. Podack, we had suggested that, as the three sequences available for perforin are not the same, it would have been useful if some attempt had been made in the book to reconcile the differences. It
(~~ 1gg0. £1sevlerSoencePubhshers Lid. UK 0167 4919/90~$02 00
References 10sband, M. and Parkman, R. (1978 J. Immunol. 121, 179-185 2 Playfair, J.H.L. and Krsiakova, M. (1969) Transplantation 7,443J],44
has been Drought to our attention that two of the sequences were not yet published at the time that the book was written - a lapse on our part for which we would like to apologize to Dr Podack.
David M. Ojcius John Ding-E Young Laboratory of Cellular Physiologyand Immunology, The RockefellerUniversity, 1230 York Ave, New York, NY 10021, USA.
107
Comments on syngeneic GVHD Sir, In his shor~ review on 'Graft-versushost disease: an alternative hypothesis' (Immunol. Today, 1989, 10, 362-364), Parkman discussed among other issues some aspects of syngeneic GVHD. The author referred to an article by Glazier and coworkers ~ as the first demonstration of syngeneic GVHD in adult animals. These experiments dealt with Cyclosporin-A-induc,:d GVHD which occurred only after total body irradiation (TBI) that included the thymus, which suqgested that damage to t ~'- thynuc stroma was a ,~'quirement for the devek,..')ment of synqeneic GVHD. Parkman also refers to similar clinical syndromes observed by Cheney and Sprent 2 in neonatally thymectomized and CyclosporinA-treated mice. This review is incomplete, in that it ignores many previous reports on GVHD such as symptomat,~logy in the absence of a bone marrow 9raft of foreign origin. A disease termed isologous secondary disease (iselogous was used for syngeneic and secondary disease was used for what later became known as GVHD) was described more than twenty years earlier in mice surviving high lethal dose T8! and rescue w!th small numbers of syngeneic bone marrow cells 3-s and in mice surviving an LD8o of TBI (Refs 6,7). The histopathological changes in these mice were similar to those of allogeneic GVHD, but generally less severe. Histological analysis of the thymus 8 revealed an ;rreversible decrease in the number of epithelial cells of the thymus and the disease could be prevented by implantation of syngeneic newborn thymus fr3gments after the TBI and bone marrow transplantation 9. These thymus grafts were pre-irradiated to inactivate the T lymphocytes. Just as in the case of Cyclosporin-A-induced syngeneic GVHD, all the evidence pointed to 'thymic stromal damage' as a causative factor. As regards the occurrence of similar syndromes in neonataiiy thymectomized mice, there is exteqsive literature on autoimmunp reactions in these animals, without additional treatment with Cyclosporin A. This so-called post-thyrr~ectomy syndrome was already described in 1964 (Ref.
10) and shortly afterwards confirmed and extended by Monier ~ ~,. More recently it was also reported in thymectomized adult mice subjected to sublethal TBI (Ref. 14). All these original observations are accessible via modern reviews is. The different experimental conditions that were found to provoke syngeneic and autologous GVHD provide interesting opportunities for a re-analysis with the help of modern reagents.
D.W. van Bekkum Radlobiological Institute TNO, PO Box 5815, 2280 HV Rijswijk, The Netherlands.
References 1 Glazier, A., Tutschka, PJ., Farner, E.R. et al. (1983)J. Exp. Med. 158, 1-8 2 Cheney, R.T. and Sprent, J. (1985) Transplant. Proc. 17, 528-530 3 Barnes, D.W.H., Ford, C.E., Ilbery, P.L.T. et al. (1957) J. Cell. Comp. Physiol. 50, 123 4 Van Bekkum, D.W., Vos, O. and Weyzen, W.W.H. (1959)J. Natl Cancer Inst. 23, 75-89 5 Barnes, D.W.H., Loutit, J.F. and Micklem, HS. (1962)in Mechanisms of
Immunological Tolerance (Hasek, M, Lengerova, A. and Vqtlskova, M., eds), p. 371, Publishing House of the Czechoslovak Academy of Sciences 6 Mole, R.H. (1956) Br. J. Racliol. 29, 563-569 7 Corp, M.J. and Neal, F.E. (1959) Int. J. Radiat. Biol. 1,256-265 8 Van Bekkum, D.W. (1967) Brookhaven Symp Biol. 20, 190-211 9 Van Bekkum, D.W. (1969)iq Comparative Cellular and Species Radiosensitivity (Bond, V.P. and Sugahara, T., eds), pp. 175-192, Igaku Shoin 10 De Vries, M.J., Van Putten, L.M., Balner, H. et al. (t964)Rev. Fr Etud. Clin. Biol. 9, 381-397 11 Thivolet, J. and Monier, J.C. (1969) Rev. Ft. Etud. Clin. Biol. 14, 132-143 12 Monier, J.C., Thivolet, J., Sepetjian, M. (1969) Rev. Ft. Etud. Clin. Biol. 14, t85-188 13 Monier, J.C. (1972) Contr61e par ie Thymus et les Cellu~es T, des Phenomenes d'Auto Immunisation et de Competition Antigenique, Ediprim 14 Ansar Ahmed, S. and Penhale, W.J. (1981) Experientia 37, 1341-1343 15 Van Bekkum, D.W. and LSwenberg, B., eds (1985) Bone Marrow Transplantation: Biological Mechanisms and Clinical Practice, Marcel Dekker
Autoreactive T cells and graft-versus-host disease
in NZB mice fits in well with Park!!lan's suggestion of an autgregula"(ion oetect.
R. Parkman (Immunol. Today, 1989, 10, 362-364 and Ref. 1) has drawn attention to the possibility that autoreactive T cells may be partly respon sible for initiating GVH disease, and quotes experiments on syngeneic splenomegaly. This phenomenon was first reported some years earlier 2 and the fact that it was most marked
Department of Imr~unology, University College and MiddlesexSchoolof Medicine,Arthur Stanley House, 40-50 Tottenham Street, London WIP 9PG, UK.
John Playfair
Sir,
Cytotoxic effector mechanisms Sir, In our recent book review of Current Topics in Microbiology and Immunology: Cytotoxic Effector Mechanisms, edited by E.R. Podack, we had suggested that, as the three sequences available for perforin are not the same, it would have been useful if some attempt had been made in the book to reconcile the differences. It
(~~ 1gg0. £1sevlerSoencePubhshers Lid. UK 0167 4919/90~$02 00
References 10sband, M. and Parkman, R. (1978 J. Immunol. 121, 179-185 2 Playfair, J.H.L. and Krsiakova, M. (1969) Transplantation 7,443J],44
has been Drought to our attention that two of the sequences were not yet published at the time that the book was written - a lapse on our part for which we would like to apologize to Dr Podack.
David M. Ojcius John Ding-E Young Laboratory of Cellular Physiologyand Immunology, The RockefellerUniversity, 1230 York Ave, New York, NY 10021, USA.
107