Rapid T cell repopulation after rabbit anti-thymocyte globulin (rATG) treatment is driven mainly by cytomegalovirus
| Autor: | S. L. Yong, K. A. M. I. van Donselaar-van der Pant, R. A. W. Van Lier, Ester B. M. Remmerswaal, I. J. M. ten Berge, Simone H. C. Havenith, F. J. Bemelman |
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| Přispěvatelé: | Other departments, Amsterdam institute for Infection and Immunity, Experimental Immunology, Nephrology, Landsteiner Laboratory |
| Rok vydání: | 2012 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Graft Rejection Male Human cytomegalovirus T cell Immunology Cytomegalovirus CD8-Positive T-Lymphocytes Biology Antiviral Agents Young Adult Postoperative Complications Betaherpesvirinae Lymphopenia medicine Animals Humans Valganciclovir Immunology and Allergy Lymphocyte Count Viremia Gene Rearrangement beta-Chain T-Cell Antigen Receptor Ganciclovir Antilymphocyte Serum Interleukin-7 virus diseases Interleukin Original Articles T lymphocyte Middle Aged medicine.disease biology.organism_classification Kidney Transplantation Virology Anti-thymocyte globulin medicine.anatomical_structure Cytomegalovirus Infections DNA Viral Female Virus Activation Rabbits Lymphocytopenia Immunosuppressive Agents CD8 |
| Zdroj: | Clinical and experimental immunology, 169(3), 292-301. Wiley-Blackwell |
| ISSN: | 1365-2249 0009-9104 |
| DOI: | 10.1111/j.1365-2249.2012.04622.x |
| Popis: | Summary Rabbit anti-thymocyte globulin (rATG) induces a long-lasting lymphocytopenia. CD4+ T cells remain depleted for up to 2 years, whereas the CD8+ T cell compartment is refilled rapidly by highly differentiated CD27–CD45RA+CD57+effector-type cells. Because the presence of these highly differentiated CD8+ T cells has been associated with cytomegalovirus (CMV) infection, we questioned to what extent restoration of CMV T cell immunity contributes to the re-emergence of T cells following rATG treatment. We compared T cell repopulation in six CMV-seropositive patients with CMV reactivation (reactivating CMV+) to that in three CMV+ patients without reactivation (non-reactivating CMV+), and to that in three CMV-seronegative recipients receiving a kidney from a CMV-seronegative donor (CMV−/−). All patients received rATG because of acute allograft rejection. Total CD4 and CD8 counts, frequency and phenotype of virus-specific CD8+ T cells were determined. In reactivating CMV+ patients, total CD8+ T cells reappeared rapidly, whereas in non-reactivating CMV+ patients they lagged behind. In CMV−/− patients, CD8+ T cell counts had not yet reached pretransplant levels after 2 years. CMV reactivation was indeed followed by a progressive accumulation of CMV-specific CD8+ T cells. During lymphocytopenia following rATG treatment, serum interleukin (IL)-7 levels were elevated. Although this was most prominent in the CMV-seronegative patients, it did not result in an advantage in T cell repopulation in these patients. Repopulated CD8+ T cells showed increased skewing in their Vβ repertoire in both CMV−/− and reactivating CMV-seropositive patients. We conclude that rapid T cell repopulation following rATG treatment is driven mainly by CMV. |
| Databáze: | OpenAIRE |
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