Dynamics of Lymphocyte Reconstitution after Hematopoietic Transplantation during Chronic Lymphocytic Choriomeningitis Virus Infection

Mitra Bhattacharyya, Pablo Penaloza-MacMaster*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Bone marrow transplantation is a treatment for various cancers and genetic diseases, and the only case of a cured HIV infection involved the use of this clinical procedure, highlighting the potential use of this therapy for curing many chronic diseases. However, little is known about how chronic viral infection influences lymphocyte reconstitution after bone marrow transplantation. To address this, we infected mice with chronic lymphocytic choriomeningitis virus, and performed bone marrow transplantation to assess lymphocyte reconstitution. Interestingly, we observed that adoptively transferred marrow cells exhibited preferential B cell differentiation in chronically infected mice. Moreover, donor marrow cells that were adoptively transferred into chronically infected mice differentiated into virus-specific CD8 T cells that were able to expand after PD-L1 blockade. Taken together, our data show that chronic viral infection induces a biased differentiation of bone marrow stem cells into B cells, and that exhausted virus-specific CD8 T cells generated de novo in this setting are rescuable by PD-1 blockade. These data contribute to the understanding of how chronic viral infection impacts lymphocyte reconstitution, and may provide valuable information to improve current hematopoietic transplantation regimens in chronically infected hosts.

Original languageEnglish (US)
Pages (from-to)430-438
Number of pages9
JournalAIDS research and human retroviruses
Volume34
Issue number5
DOIs
StatePublished - May 1 2018

Keywords

  • LCMV
  • T cell immunity
  • cell mediated immunity
  • hematopoietic transplantation
  • immune exhaustion
  • viral pathogenesis

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Dynamics of Lymphocyte Reconstitution after Hematopoietic Transplantation during Chronic Lymphocytic Choriomeningitis Virus Infection'. Together they form a unique fingerprint.

  • Cite this