title: Effects of immunosuppression on circulating adeno-associated virus capsid-specific T cells in humans.
abstract: In humans adeno-associated virus (AAV)-mediated gene transfer is followed by expansion of AAV capsid-specific T cells, evidence of cell damage, and loss of transgene product expression, implicating immunological rejection of vector-transduced cells, which may be prevented by immunosuppressive drugs. We undertook this study to assess the effect of immunosuppression (IS) used for organ transplantation on immune responses to AAV capsid antigens. Recipients of liver or kidney transplants were tested before and 4 weeks after induction of IS in comparison with matched samples from healthy human adults and an additional cohort with comorbid conditions similar to those of the transplant patients. Our data show that transplant patients and comorbid control subjects have markedly higher frequencies of circulating AAV capsid-specific T cells compared with healthy adults. On average, IS resulted in a reduction of AAV-specific CD4⁺ T cells, whereas numbers of circulating CD8⁺ effector and central memory T cells tended to increase. Independent of the type of transplant or the IS regimens, the trend of AAV capsid-specific T cell responses after drug treatment varied; in some patients responses were unaffected whereas others showed decreases or even pronounced increases, casting doubt on the usefulness of prophylactic IS for AAV vector recipients.
authors: Wistar Institute, Philadelphia, PA 19104, USA.
authors: Elizabeth M
authors: EM
authors: Parzych
authors: Hua
authors: H
authors: Li
authors: Xiangfan
authors: X
authors: Yin
authors: Qin
authors: Q
authors: Liu
authors: Te-Lang
authors: TL
authors: Wu
authors: Gregory M
authors: GM
authors: Podsakoff
authors: Katherine A
authors: KA
authors: High
authors: Matthew H
authors: MH
authors: Levine
authors: Hildegund C J
authors: HC
authors: Ertl
mesh_terms: D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002213:Capsid / Q000276:immunology; D016022:Case-Control Studies; D000229:Dependovirus / Q000235:genetics* / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D016030:Kidney Transplantation; D008099:Liver / Q000276:immunology / Q000378:metabolism; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D014181:Transplantation Immunology
chemical_list: D000956:Antigens, Viral