- Email: [email protected]
Urine test to monitor kidney-transplant rejection
News & Comment
sites. Lead author Richard Stiehm, Professor of Pediatrics at Mattel Children’s Hospital at UCLA, CA, USA explained in a press release, ‘most children born with these immune deficiencies die at an early age and nearly all succumb in young adulthood’. Advantages of using cord blood over bone marrow include: the fact that it is never infected with Epstein–Barr virus, which can cause problems in XLP; fewer problems with graft-versus-host disease; the ready availability of cryopreserved cord blood (within two weeks of donor identification); and the fact that histoincompatibility is better tolerated with cord blood than bone marrow. The UCLA umbilical cord-blood bank was set up with $10 million from the NIH as part of a program to investigate the efficacy and viability of cord-blood transplants. J. Pediatr. (2001) 138, 570–573 HM
TRENDS in Immunology Vol.22 No.6 June 2001
infused with bone marrow from the living donors at the time of transplantation, and three months after surgery, immunosuppression was stopped. One patient has been free of immunosuppressive therapy for 30 months and the other for six months, with no signs of graft damage. Clinical trials are to begin in patients with kidney failure and multiple myeloma, and also in patients with uncomplicated kidney transplants. HM
Urine test to monitor kidneytransplant rejection
Kidney transplants survive withdrawal of immunosuppression Speaking at the Experimental Biology 2001 meeeting in Orlando, FL, USA, Benedict Cosimi of Harvard Medical School announced that, following the induction of mixed chimerism, two kidney-transplant recipients have been able to discontinue immunosuppressive therapy. Patients were
A urine test that diagnoses acute rejection without the need for an invasive biopsy
299
successfully predicted acute rejection in 83% of the 85 patients tested. Researchers at the Weill Medical College of Cornell University, USA, led by Manikkam Suthanthiran, used PCR to measure mRNA levels for perforin and granzyme B, both of which are found in the cytotoxic T cells prevalent in grafts during acute rejection. It is hoped that this test will lead to the earlier diagnosis of rejection episodes, before tissue damage occurs. Approximately 35% of kidney-transplant patients will experience a rejection episode during the first year, making graft survival for more than one year 20% less probable. In an editorial to accompany publication of the results, Jean-Paul Soulillou states that repeated urine tests, ‘may provide a unique opportunity to detect subclinical episodes of rejection that may culminate in chronic rejection’. New Engl. J. Med. (2001) 344, 947–954 HM
This month’s In Brief articles were compiled by Hilary Marshall ([email protected]) and Luke O’Neill ([email protected])
Letters
β1 paradox The TGF-β in asthma In his recent article, Atsuhito Nakao reviewed evidence that transforming growth factor (TGF)-β1 might be important for the suppression of asthma1. Nakao cited strong evidence from mouse models involving manipulations that either increase the production of TGF-β1 by regulatory T cells2 or that block the response of T cells to TGF-β1 (Ref. 3). He then pointed out that levels of TGF-β1 are abnormally high in the airways of human asthmatics, where the cytokine is probably released from eosinophils and bronchial epithelial cells4. This was presented as a paradox, but I would suggest otherwise. We should not think of individual cytokines in isolation from their context or cell of origin. A cytokine is a word in a sentence, not an independently
acting signal. TGF-β1 is clearly involved in immunopathological processes as well as in immunoregulation. It is likely to participate in the important fibrosis and tissue remodeling seen in asthma4. By contrast, it is associated with immunoregulation when it is produced by regulatory T cells, acting together with the numerous other functions that regulatory T cells perform, some of which require cell–cell interactions5. This argument is even clearer in relation to interleukin (IL)-4, where the same apparent paradox is seen. Many authors describe IL-4 as an antiinflammatory cytokine, to the despair of workers in the fields of allergy, idiopathic pulmonary fibrosis6 and infectious disease, where IL-4 plays a central role in immunopathology7–9. For IL-4, the paradox disappears if we remember that an IL-4-secreting T helper 2 (Th2) effector cell can cause damage, whereas an IL-4-
expressing regulatory T cell can indeed be anti-inflammatory. In short, the time might have come to stop talking about the ‘cytokine balance’. We should always consider the nature of the cell that is secreting the cytokine and the other simultaneous functions of that cell. Graham A.W. Rook Dept of Medical Microbiology, Windeyer Institute of Medical Sciences, Royal Free and University College Medical School, 46 Cleveland Street, London, UK W1T 4JF. e-mail: [email protected] References 1 Nakao, A. (2001) Is TGF-β1 the key to suppression of human asthma? Trends Immunol. 22, 115–118 2 Haneda, K. et al. (1997) TGF-β induced by oral tolerance ameliorates experimental tracheal eosinophilia. J. Immunol. 159, 4484–4490 3 Nakao, A. et al. (2000) Blockade of TGF-β/Smad signaling in T cells by overexpression of Smad7 enhances antigen-induced airway inflammation and airway reactivity. J. Exp. Med. 192, 151–158
http://immunology.trends.com 1471-4906/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.
sites. Lead author Richard Stiehm, Professor of Pediatrics at Mattel Children’s Hospital at UCLA, CA, USA explained in a press release, ‘most children born with these immune deficiencies die at an early age and nearly all succumb in young adulthood’. Advantages of using cord blood over bone marrow include: the fact that it is never infected with Epstein–Barr virus, which can cause problems in XLP; fewer problems with graft-versus-host disease; the ready availability of cryopreserved cord blood (within two weeks of donor identification); and the fact that histoincompatibility is better tolerated with cord blood than bone marrow. The UCLA umbilical cord-blood bank was set up with $10 million from the NIH as part of a program to investigate the efficacy and viability of cord-blood transplants. J. Pediatr. (2001) 138, 570–573 HM
TRENDS in Immunology Vol.22 No.6 June 2001
infused with bone marrow from the living donors at the time of transplantation, and three months after surgery, immunosuppression was stopped. One patient has been free of immunosuppressive therapy for 30 months and the other for six months, with no signs of graft damage. Clinical trials are to begin in patients with kidney failure and multiple myeloma, and also in patients with uncomplicated kidney transplants. HM
Urine test to monitor kidneytransplant rejection
Kidney transplants survive withdrawal of immunosuppression Speaking at the Experimental Biology 2001 meeeting in Orlando, FL, USA, Benedict Cosimi of Harvard Medical School announced that, following the induction of mixed chimerism, two kidney-transplant recipients have been able to discontinue immunosuppressive therapy. Patients were
A urine test that diagnoses acute rejection without the need for an invasive biopsy
299
successfully predicted acute rejection in 83% of the 85 patients tested. Researchers at the Weill Medical College of Cornell University, USA, led by Manikkam Suthanthiran, used PCR to measure mRNA levels for perforin and granzyme B, both of which are found in the cytotoxic T cells prevalent in grafts during acute rejection. It is hoped that this test will lead to the earlier diagnosis of rejection episodes, before tissue damage occurs. Approximately 35% of kidney-transplant patients will experience a rejection episode during the first year, making graft survival for more than one year 20% less probable. In an editorial to accompany publication of the results, Jean-Paul Soulillou states that repeated urine tests, ‘may provide a unique opportunity to detect subclinical episodes of rejection that may culminate in chronic rejection’. New Engl. J. Med. (2001) 344, 947–954 HM
This month’s In Brief articles were compiled by Hilary Marshall ([email protected]) and Luke O’Neill ([email protected])
Letters
β1 paradox The TGF-β in asthma In his recent article, Atsuhito Nakao reviewed evidence that transforming growth factor (TGF)-β1 might be important for the suppression of asthma1. Nakao cited strong evidence from mouse models involving manipulations that either increase the production of TGF-β1 by regulatory T cells2 or that block the response of T cells to TGF-β1 (Ref. 3). He then pointed out that levels of TGF-β1 are abnormally high in the airways of human asthmatics, where the cytokine is probably released from eosinophils and bronchial epithelial cells4. This was presented as a paradox, but I would suggest otherwise. We should not think of individual cytokines in isolation from their context or cell of origin. A cytokine is a word in a sentence, not an independently
acting signal. TGF-β1 is clearly involved in immunopathological processes as well as in immunoregulation. It is likely to participate in the important fibrosis and tissue remodeling seen in asthma4. By contrast, it is associated with immunoregulation when it is produced by regulatory T cells, acting together with the numerous other functions that regulatory T cells perform, some of which require cell–cell interactions5. This argument is even clearer in relation to interleukin (IL)-4, where the same apparent paradox is seen. Many authors describe IL-4 as an antiinflammatory cytokine, to the despair of workers in the fields of allergy, idiopathic pulmonary fibrosis6 and infectious disease, where IL-4 plays a central role in immunopathology7–9. For IL-4, the paradox disappears if we remember that an IL-4-secreting T helper 2 (Th2) effector cell can cause damage, whereas an IL-4-
expressing regulatory T cell can indeed be anti-inflammatory. In short, the time might have come to stop talking about the ‘cytokine balance’. We should always consider the nature of the cell that is secreting the cytokine and the other simultaneous functions of that cell. Graham A.W. Rook Dept of Medical Microbiology, Windeyer Institute of Medical Sciences, Royal Free and University College Medical School, 46 Cleveland Street, London, UK W1T 4JF. e-mail: [email protected] References 1 Nakao, A. (2001) Is TGF-β1 the key to suppression of human asthma? Trends Immunol. 22, 115–118 2 Haneda, K. et al. (1997) TGF-β induced by oral tolerance ameliorates experimental tracheal eosinophilia. J. Immunol. 159, 4484–4490 3 Nakao, A. et al. (2000) Blockade of TGF-β/Smad signaling in T cells by overexpression of Smad7 enhances antigen-induced airway inflammation and airway reactivity. J. Exp. Med. 192, 151–158
http://immunology.trends.com 1471-4906/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.