The Detailed Kinetics of Cytomegalovirus-specific T cell Responses after Hematopoietic Stem Cell Transplantation: 1 Year Follow-up Data
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
The detailed kinetics of the cytomegalovirus (CMV)-specific T cell response in hematopoietic stem cell transplant (HCT) recipients have not yet been fully assessed. We evaluated these kinetics of CMV-specific T cell response and factors associated with high CMV-specific T cell responses 1 year after HCT. In HCT recipients, CMV pp65 and IE1-specific ELISPOT assay were performed before HCT (D0), and at 30 (D30), 90 (D90), 180 (D180), and 360 (D360) days after HCT. Of the 51 HCT recipients with donor-positive (D+)/recipient-positive (R+) serology, 26 (51%) developed CMV infections after HCT. The patterns of post-transplantation reconstitution for CMV-specific T cell response were classified into 4 types: 1) an initial decrease at D30 followed by gradual T cell reconstitution without CMV infection (35%), 2) an initial decrease at D30 followed by gradual T cell reconstitution preceded by CMV infection (35%), 3) failure of gradual or constant T cell reconstitution (26%), and 4) no significant T cell reconstitution (4%). There was no significant difference between ELISPOT counts of D360 and those of D0. High CMV-specific T cell responses at D360 were not associated with high CMV-specific T cell response at D0, CMV infection, ganciclovir therapy, graft versus host disease (GVHD), and immunosuppressant use. In conclusion, there are 4 distinct patterns of reconstitution of the CMV-specific T cell response after HCT. In addition, reconstituted donor-origin CMV-specific T cell responses appeared to be constant until day 360 after HCT, regardless of the level of the pre-transplant CMV-specific T cell response, CMV infection, and immunosuppressant use.
Abstract
The detailed kinetics of the cytomegalovirus (CMV)-specific T cell response in hematopoietic stem cell transplant (HCT) recipients have not yet been fully assessed. We evaluated these kinetics of CMV-specific T cell response and factors associated with high CMV-specific T cell responses 1 year after HCT. In HCT recipients, CMV pp65 and IE1-specific ELISPOT assay were performed before HCT (D0), and at 30 (D30), 90 (D90), 180 (D180), and 360 (D360) days after HCT. Of the 51 HCT recipients with donor-positive (D+)/recipient-positive (R+) serology, 26 (51%) developed CMV infections after HCT. The patterns of post-transplantation reconstitution for CMV-specific T cell response were classified into 4 types: 1) an initial decrease at D30 followed by gradual T cell reconstitution without CMV infection (35%), 2) an initial decrease at D30 followed by gradual T cell reconstitution preceded by CMV infection (35%), 3) failure of gradual or constant T cell reconstitution (26%), and 4) no significant T cell reconstitution (4%). There was no significant difference between ELISPOT counts of D360 and those of D0. High CMV-specific T cell responses at D360 were not associated with high CMV-specific T cell response at D0, CMV infection, ganciclovir therapy, graft versus host disease (GVHD), and immunosuppressant use. In conclusion, there are 4 distinct patterns of reconstitution of the CMV-specific T cell response after HCT. In addition, reconstituted donor-origin CMV-specific T cell responses appeared to be constant until day 360 after HCT, regardless of the level of the pre-transplant CMV-specific T cell response, CMV infection, and immunosuppressant use.
참고문헌 (17)
- Reusser P, "Cytotoxic T-lymphocyte response to cytomegalovirus after human allogeneic bone marrow transplantation: pattern of recovery and correlation with cytomegalovirus infection and disease", Blood, 78, pp.1373~1380 (1991)
- Barron MA, "Relationship of reconstituted adaptive and innate cytomegalovirus (CMV)-specific immune responses with CMV viremia in hematopoietic stem cell transplant recipients", Clin Infect Dis, 49, pp.1777~1783 (2009)[DOI]
- Boeckh M, "Cytomegalovirus pp65 antigenemia-guided early treatment with ganciclovir versus ganciclovir at engraftment after allogeneic marrow transplantation: a randomized double-blind study", Blood, 88, pp.4063~4071 (1996)
- Einsele H, "Risk factors for treatment failures in patients receiving PCR-based preemptive therapy for CMV infection", Bone Marrow Transplant, 25, pp.757~763 (2000)[DOI]
- Green ML, "Efficacy of a viral load-based, risk-adapted, preemptive treatment strategy for prevention of cytomegalovirus disease after hematopoietic cell transplantation", Biol Blood Marrow Transplant, 18, pp.1687~1699 (2012)[DOI]
- Li CR, "Recovery of HLA-restricted cytomegalovirus (CMV)-specific T-cell responses after allogeneic bone marrow transplant: correlation with CMV disease and effect of ganciclovir prophylaxis", Blood, 83, pp.1971~1979 (1994)
- Ciaurriz M, "The immune response to cytomegalovirus in allogeneic hematopoietic stem cell transplant recipients", Cell Mol Life Sci, 72, pp.4049~4062 (2015)[DOI]
- Hebart H, "Sensitive detection of human cytomegalovirus peptide-specific cytotoxic T-lymphocyte responses by interferon-gamma-enzyme-linked immunospot assay and flow cytometry in healthy individuals and in patients after allogeneic stem cell transplantation", Blood, 99, pp.3830~3837 (2002)[DOI]
- Ohnishi M, "Evaluation of cytomegalovirus-specific T-cell reconstitution in patients after various allogeneic haematopoietic stem cell transplantation using interferon-gamma-enzyme-linked immunospot and human leucocyte antigen tetramer assays with an immunodominant T-cell epitope", Br J Haematol, 131, pp.472~479 (2005)[DOI]
- Avetisyan G, "Evaluation of intervention strategy based on CMV-specific immune responses after allogeneic SCT", Bone Marrow Transplant, 40, pp.865~869 (2007)[DOI]
- Abate D, "Diagnostic utility of human cytomegalovirus-specific T-cell response monitoring in predicting viremia in pediatric allogeneic stem-cell transplant patients", Transplantation, 93, pp.536~542 (2012)[DOI]
- Ljungman P, "Long-term immunity to measles, mumps, and rubella after allogeneic bone marrow transplantation", Blood, 84, pp.657~663 (1994)
- Spoulou V, "Long-term immunity to measles, mumps and rubella after MMR vaccination among children with bone marrow transplants", Bone Marrow Transplant, 33, pp.1187~1190 (2004)[DOI]
- Lacey SF, "Assessment of cellular immunity to human cytomegalovirus in recipients of allogeneic stem cell transplants", Biol Blood Marrow Transplant, 10, pp.433~447 (2004)[DOI]
- Lehmann PV, "Unique strengths of ELISPOT for T cell diagnostics", Methods Mol Biol, 792, pp.3~23 (2012)
- Luo XH, "Immune reconstitution to cytomegalovirus following partially matched-related donor transplantation: impact of in vivo T-cell depletion and granulocyte colony-stimulating factor-primed peripheral blood", bone marrow mixed grafts, 2013, pp.15, 22~33
- Snyder LD, "Polyfunctional T-Cell signatures to predict protection from cytomegalovirus after lung transplantation", Am J Respir Crit Care Med, 193, pp.78~85 (2016)[DOI]