288
References 1 James, K. and Ritchie, W. S. (1984) Irnmunol. Today 5, 193-194 2 Timonen, T , Ortaldo, J. R. and Herberman, R. B. (1981)J. Exp. Med. 153, 569- 582 3 Brieva,J. A., Targan, S. and Stevens, R. H. (1984).]. Immunol. 132, 611-615 4 Arai, S., Yarnamoto, H., Ito, K. and Kumagai, K. (1983)J. Immunol. 131,651657 5 Tilden, A., Abo, T. and Balch, C. M. (1983)
Therapy for AIDS SIR, It is now widely accepted that the acquired immunodeficiency syndrome (AIDS) is caused by the h u m a n T-lymphotropic virus type III ( H T L V - I I I ) , which infects and destroys T4 + h e l p e r - i n d u c e r lymphocytes. Proliferation a n d consequent cytopathicity of the virus appears to occur only in T4 + cells which have u n d e r g o n e activationS; indeed, the existence of raised levels of activated T 4 + cells in the circulation and l y m p h o i d tissues o f high risk groups m a y well be a major predisposing factor for the development of the full-blown syndrome. Activated T 4 + cells will proliferate in response to interleukin 2 (IL-2), and this agent appears to partially reconstitute i m m u n e responsiveness in vitro in the cells of some A I D S patients 2 *. Consequently, several groups have used IL-2 as a potential i m m u n o restorative in vivo, even t h o u g h there would appear to be serious objections to this approach. IL-2 will e x p a n d both the activated T 4 + population, providing fertile g r o u n d for virus proliferation, and the activated T8 + subset, included a m o n g s t which are suppressors of
Immunology Today, vol. 6, No. 10, 1985 J. ImmunoL 130, 1171-1175 6 Pistoia, V., Cozzolino, F., Torcia, M., Castigli, E. and Ferrarini, M. (1985) J. Immunol. 134, 3179-3184 7 Pistoia, V., Nocera, A., Ghio, R., Leprini, A., Perata, A., Pistone, M. A. and Ferrarini, M. (1982) Exp. Hematol. 11, 249-259 8 Kasahara, T., Djeu, J. Y., Dougherty, J. F. and Oppertheim, J. J. (1983)J. Immunol. 131, 2379-2383 9 Scala, 'G., Anavena, P., Djeu, J. Y., i m m u n e effector systems. In vivo use of IL-2 may, therefore, increase rather than decrease the t e m p o of disease progression. It is most unlikely that i m m u n o reconstitution could succeed while virus remains to infect any newly induced i m m u n o c o m p e t e n t T4 + cells. C e r t a i n anti-viral agents, notably ribavirin 5 and s u r a m i n 6, have shown promise as inhibitors o f virus infectivity a n d replication in vitro, a n d are now being evaluated in pilot trials. If it should become possible to eliminate H T L V - I I I in vivo, bone m a r r o w transplantation could succeed 7, but suitable donors will not be available in most cases. H o w e v e r , autologous bone m a r r o w could be obtained at an early stage in the disease, be p u r g e d of virus-infected cells by treatm e n t in vitro with anti-viral agents, or possibly with O K T 4 monoclonal antibody to remove chronically infected cells, and be stored frozen for reinfusion at a suitable time. H e a l t h y individuals exposed to H T L V - I I I , who presumably have normal, low levels of activated T4 + cells, m a y h a r b o u r and transmit the virus while r e m a i n i n g symptom-free. It is possible that disease could develop in carriers if infected T 4 + cells become
Kasahara, T., Ortaldo, J. R., Herberrnan, R. B. and Oppenheim, J. J. (1984) Nature (London) 309, 56-59 10 Pistoia, V., Ghio, R., Nocera, A., Leprini, A., Perata, A. and Ferrarini, M. (1985)Blood 65, 464-472 11 Degli Antoni, G., Perussia, B., Mangoni, L. and Trinchieri, G. (1985)J. Exp. Med. 161, 1152-1168 12 Hanson, M., Beran, M., Anderson, B. and Kiessling, R. (1982) jr. Immunol. 129, 126-132 activated and thus supportive of virus replication. This implies that every effort should be m a d e to eliminate latent virus in healthy individuals found to have H T L V - I I I antibodies.
References 1 Montagnier, L., Chermann, J. C., Barr~Sinoussi, F. et al. (1984) in Human T-ceU lo~kaemia/lymphoma viruses (Gallo, R. C., Essex, M. and Gross, L. eds), pp. 363-379, Cold Spring Harbor Laboratories, New York 2 Gupta, S., GiUis, S., Thornton, M. and Goldberg, M. (1984) Clin. Exp. Immunol. 58, 395-401 3 Lifson, J. D., Benike, C.J., Mark, D. F., et al. (1984) Lancet i 698-702 4 Sheridan, J. F., Aurelian, L., Donnenberg, A. D. and Quinn, T. C. (1984)J. Clin. Immunol. 4, 304-311 5 McCormick, J. B., Getehen, J. P., Mitchell, S. W. and Hicks, D, R. (1984) Lancet ii, 1366-1369 6 Mitsuya, H., Popovic, M., Yarchoan, R., et al. (1984) Science 226, 172-174 7 Lane, H. C., Masur, H., Longo, D. L., etal. (1984) N. Engl. J. Med. 311, 1099-1103 BRIAN M. JONES University of Hong Kong, Department of Pathology, Queen Ma?7 Hospital Compound, Hong Kong.
Modulation of immunity by drugs SIR, In their article (Immunol. Today, 1985, 6, 115-117), J . E. Blalock and E. M . Smith misinterpret and/or misquote work done by G. Maestroni and myself and published in several journals. W e have never used a ' n e u r o p e p t i d e h o r m o n e cocktail' for successful allograft transplantation. I n our work on the pharmacological control of the i m m u n e response, we published in 1977 •a n d 1978 a series of papers ~-3 in which we d e m o n s t r a t e d that a combination of drugs, namely the alpha-blocker phentolamine, the d o p a m i n e r g i c receptor blocker haloperidol a n d the precursor of serotonin, 5-hydroxytryptophan, completely abrogated the p r i m a r y and
m e m o r y response to antigens. A com~ bination of polypeptide h o r m o n e s (adrenocorticotrophic h o r m o n e , luteotropic and follicle stimulating h o r m o n e ) could p r e v e n t the action of the three drugs. W e proposed at that time that lymphocytes act as messengers to the neuroendocrine system and that intervention with drugs acting on neuroendocrine regulation might permit the control of the i m m u n e response. H o w e v e r , since the authors o f the article m e n t i o n allograft transplantation, m a y b e they refer to another kind of approach in which bone m a r r o w - d e r i v e d factors p e r m i t the safe transplantation Of allogeneic bone m a r r o w between histoincompatible
mouse strains 4. T h e chemical nature o f the m a r r o w factors is still u n k n o w n and cannot certainly be classified as ' n e u r o peptide h o r m o n e cocktail'. [z]-]
References 1 Pierpaoli, W. and Maestroni, G. J. M. (1977) Cell Imraunol. 31,355-363 2 Pierpaoli, W. and Maestroni, G. J. M. (1978) Immunology 34, 419-430 3 Pierpaoli, W. and Maestroni, G. J. M. (1978).], Immunol. 120, 1600-1603 4 Pierpaoli, W., Maestroni, G. J. M. and Saehe, E. (1981) Cell Immunol. 57, 219-228 WALTER PIERPAOLI Institute for Integrative Biomedical Research, CH-8123 Ebmatingen, Lohwisstrasse 50, Switzerland.
References 1 James, K. and Ritchie, W. S. (1984) Irnmunol. Today 5, 193-194 2 Timonen, T , Ortaldo, J. R. and Herberman, R. B. (1981)J. Exp. Med. 153, 569- 582 3 Brieva,J. A., Targan, S. and Stevens, R. H. (1984).]. Immunol. 132, 611-615 4 Arai, S., Yarnamoto, H., Ito, K. and Kumagai, K. (1983)J. Immunol. 131,651657 5 Tilden, A., Abo, T. and Balch, C. M. (1983)
Therapy for AIDS SIR, It is now widely accepted that the acquired immunodeficiency syndrome (AIDS) is caused by the h u m a n T-lymphotropic virus type III ( H T L V - I I I ) , which infects and destroys T4 + h e l p e r - i n d u c e r lymphocytes. Proliferation a n d consequent cytopathicity of the virus appears to occur only in T4 + cells which have u n d e r g o n e activationS; indeed, the existence of raised levels of activated T 4 + cells in the circulation and l y m p h o i d tissues o f high risk groups m a y well be a major predisposing factor for the development of the full-blown syndrome. Activated T 4 + cells will proliferate in response to interleukin 2 (IL-2), and this agent appears to partially reconstitute i m m u n e responsiveness in vitro in the cells of some A I D S patients 2 *. Consequently, several groups have used IL-2 as a potential i m m u n o restorative in vivo, even t h o u g h there would appear to be serious objections to this approach. IL-2 will e x p a n d both the activated T 4 + population, providing fertile g r o u n d for virus proliferation, and the activated T8 + subset, included a m o n g s t which are suppressors of
Immunology Today, vol. 6, No. 10, 1985 J. ImmunoL 130, 1171-1175 6 Pistoia, V., Cozzolino, F., Torcia, M., Castigli, E. and Ferrarini, M. (1985) J. Immunol. 134, 3179-3184 7 Pistoia, V., Nocera, A., Ghio, R., Leprini, A., Perata, A., Pistone, M. A. and Ferrarini, M. (1982) Exp. Hematol. 11, 249-259 8 Kasahara, T., Djeu, J. Y., Dougherty, J. F. and Oppertheim, J. J. (1983)J. Immunol. 131, 2379-2383 9 Scala, 'G., Anavena, P., Djeu, J. Y., i m m u n e effector systems. In vivo use of IL-2 may, therefore, increase rather than decrease the t e m p o of disease progression. It is most unlikely that i m m u n o reconstitution could succeed while virus remains to infect any newly induced i m m u n o c o m p e t e n t T4 + cells. C e r t a i n anti-viral agents, notably ribavirin 5 and s u r a m i n 6, have shown promise as inhibitors o f virus infectivity a n d replication in vitro, a n d are now being evaluated in pilot trials. If it should become possible to eliminate H T L V - I I I in vivo, bone m a r r o w transplantation could succeed 7, but suitable donors will not be available in most cases. H o w e v e r , autologous bone m a r r o w could be obtained at an early stage in the disease, be p u r g e d of virus-infected cells by treatm e n t in vitro with anti-viral agents, or possibly with O K T 4 monoclonal antibody to remove chronically infected cells, and be stored frozen for reinfusion at a suitable time. H e a l t h y individuals exposed to H T L V - I I I , who presumably have normal, low levels of activated T4 + cells, m a y h a r b o u r and transmit the virus while r e m a i n i n g symptom-free. It is possible that disease could develop in carriers if infected T 4 + cells become
Kasahara, T., Ortaldo, J. R., Herberrnan, R. B. and Oppenheim, J. J. (1984) Nature (London) 309, 56-59 10 Pistoia, V., Ghio, R., Nocera, A., Leprini, A., Perata, A. and Ferrarini, M. (1985)Blood 65, 464-472 11 Degli Antoni, G., Perussia, B., Mangoni, L. and Trinchieri, G. (1985)J. Exp. Med. 161, 1152-1168 12 Hanson, M., Beran, M., Anderson, B. and Kiessling, R. (1982) jr. Immunol. 129, 126-132 activated and thus supportive of virus replication. This implies that every effort should be m a d e to eliminate latent virus in healthy individuals found to have H T L V - I I I antibodies.
References 1 Montagnier, L., Chermann, J. C., Barr~Sinoussi, F. et al. (1984) in Human T-ceU lo~kaemia/lymphoma viruses (Gallo, R. C., Essex, M. and Gross, L. eds), pp. 363-379, Cold Spring Harbor Laboratories, New York 2 Gupta, S., GiUis, S., Thornton, M. and Goldberg, M. (1984) Clin. Exp. Immunol. 58, 395-401 3 Lifson, J. D., Benike, C.J., Mark, D. F., et al. (1984) Lancet i 698-702 4 Sheridan, J. F., Aurelian, L., Donnenberg, A. D. and Quinn, T. C. (1984)J. Clin. Immunol. 4, 304-311 5 McCormick, J. B., Getehen, J. P., Mitchell, S. W. and Hicks, D, R. (1984) Lancet ii, 1366-1369 6 Mitsuya, H., Popovic, M., Yarchoan, R., et al. (1984) Science 226, 172-174 7 Lane, H. C., Masur, H., Longo, D. L., etal. (1984) N. Engl. J. Med. 311, 1099-1103 BRIAN M. JONES University of Hong Kong, Department of Pathology, Queen Ma?7 Hospital Compound, Hong Kong.
Modulation of immunity by drugs SIR, In their article (Immunol. Today, 1985, 6, 115-117), J . E. Blalock and E. M . Smith misinterpret and/or misquote work done by G. Maestroni and myself and published in several journals. W e have never used a ' n e u r o p e p t i d e h o r m o n e cocktail' for successful allograft transplantation. I n our work on the pharmacological control of the i m m u n e response, we published in 1977 •a n d 1978 a series of papers ~-3 in which we d e m o n s t r a t e d that a combination of drugs, namely the alpha-blocker phentolamine, the d o p a m i n e r g i c receptor blocker haloperidol a n d the precursor of serotonin, 5-hydroxytryptophan, completely abrogated the p r i m a r y and
m e m o r y response to antigens. A com~ bination of polypeptide h o r m o n e s (adrenocorticotrophic h o r m o n e , luteotropic and follicle stimulating h o r m o n e ) could p r e v e n t the action of the three drugs. W e proposed at that time that lymphocytes act as messengers to the neuroendocrine system and that intervention with drugs acting on neuroendocrine regulation might permit the control of the i m m u n e response. H o w e v e r , since the authors o f the article m e n t i o n allograft transplantation, m a y b e they refer to another kind of approach in which bone m a r r o w - d e r i v e d factors p e r m i t the safe transplantation Of allogeneic bone m a r r o w between histoincompatible
mouse strains 4. T h e chemical nature o f the m a r r o w factors is still u n k n o w n and cannot certainly be classified as ' n e u r o peptide h o r m o n e cocktail'. [z]-]
References 1 Pierpaoli, W. and Maestroni, G. J. M. (1977) Cell Imraunol. 31,355-363 2 Pierpaoli, W. and Maestroni, G. J. M. (1978) Immunology 34, 419-430 3 Pierpaoli, W. and Maestroni, G. J. M. (1978).], Immunol. 120, 1600-1603 4 Pierpaoli, W., Maestroni, G. J. M. and Saehe, E. (1981) Cell Immunol. 57, 219-228 WALTER PIERPAOLI Institute for Integrative Biomedical Research, CH-8123 Ebmatingen, Lohwisstrasse 50, Switzerland.
