Reconstitution of Human Cytomegalovirus-Specific CD4+ T Cells is Critical for Control of Virus Reactivation in Hematopoietic Stem Cell Transplant Recipients but Does Not Prevent Organ Infection.

Abstract

The relative contribution of human cytomegalovirus (HMCV)-specific CD4(+) and CD8(+) T cells to the control of HCMV infection in hematopoietic stem cell transplant (HSCT) recipients is still controversial. HCMV reactivation and HCMV-specific CD4(+) and CD8(+) T cell reconstitution were monitored for 1 year in 63 HCMV-seropositive patients receiving HSCT. HCMV reactivation was detected in all but 2 patients. In 20 of 63 (31.7%) patients (group 1) HCMV infection resolved spontaneously, whereas 32 of 63 (50.8%) patients (group 2) controlled the infection after a single short-course of pre-emptive therapy and the remaining 9 (14.3%) patients (group 3) suffered from relapsing episodes of HCMV infection, requiring multiple courses of antiviral therapy. The kinetics and magnitude of HCMV-specific CD8(+) T cell reconstitution were comparable among the 3 groups, but HCMV-specific CD4(+) T cells were lower in number in patients requiring antiviral treatment. HCMV-seronegative donors, as well as unrelated donors (receiving antithymocyte globulin) and acute graft-versus-host disease (GVHD) were associated with both delayed HCMV-specific CD4(+) T cell reconstitution and severity of infection. Conversely, these risk factors had no impact on HCMV-specific CD8(+) T cells. Eight patients with previous GVHD suffered from HCMV gastrointestinal disease, although in the presence of HCMV-specific CD4(+) and CD8(+) systemic immunity and undetectable HCMV DNA in blood. Reconstitution of systemic HCMV-specific CD4(+) T cell immunity is required for control of HCMV reactivation in adult HSCT recipients, but it may not be sufficient to prevent late-onset organ localization in patients with GVHD. HCMV-specific CD8(+) T cells contribute to control of HCMV infection, but only after HCMV-specific CD4(+) T cell reconstitution.

• Authors: Elisa Gabanti, Daniele Lilleri, Francesco Ripamonti, Francesca Bruno, Paola Zelini, Milena Furione, Anna A Colombo, Emilio P Alessandrino, Giuseppe Gerna
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 21 Issue 12 Pg. 2192-2202 (Dec 2015) ISSN: 1523-6536 [Electronic] United States
• PMID: 26260678 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Antiviral Agents

Topics

• Adult
• Aged
• Antineoplastic Agents (therapeutic use)
• Antiviral Agents (therapeutic use)
• CD4-Positive T-Lymphocytes (drug effects, immunology, pathology, virology)
• CD8-Positive T-Lymphocytes (drug effects, immunology, pathology, virology)
• Cell Proliferation
• Chronic Disease
• Cytomegalovirus (immunology, pathogenicity)
• Cytomegalovirus Infections (drug therapy, immunology, mortality, pathology)
• Female
• Graft vs Host Disease (drug therapy, immunology, mortality, pathology)
• Hematologic Neoplasms (drug therapy, immunology, mortality, pathology)
• Hematopoietic Stem Cell Transplantation
• Humans
• Male
• Middle Aged
• Retrospective Studies
• Risk Factors
• Survival Analysis
• Transplantation, Homologous
• Treatment Outcome
• Virus Activation