Undernutrition and Hypoleptinemia Modulate Alloimmunity and CMV-specific Viral Immunity in Transplantation.

Journal Article (Journal Article)

BACKGROUND: Immunological mechanisms linking undernutrition to infection and the alloimmune response are poorly understood in transplantation. We aimed to determine how undernutrition and hypoleptinemia impact T-cell allospecific and cytomegalovirus (CMV) viral-specific immunity in a murine model. METHODS: Fed, fasted for 48 h (model of undernutrition), and fasted with leptin injections (leptin rescue), C57BL/6 mice received skin grafts from either C57BL/6 (syngeneic) or BALB/c (allogeneic) mice donors. Allograft rejection and survival were monitored. Fed, fasted, and leptin rescue C57BL/6 mice were inoculated with murine cytomegalovirus (mCMV). Mouse spleens were retrieved for T-cell flow cytometry analysis, mCMV DNA extraction, and quantitative polymerase chain reaction. Serum leptin levels were measured with ELISA. RESULTS: Fasted mice had prolonged rejection-free and graft survival compared with fed mice (P = 0.0002 and P = 0.043). Leptin administration did not alter rejection-free survival or allograft failure. CD8+ central memory T cell and CD8+ effector T cell proportions were significantly lower in fasted mice receiving allogeneic skin transplants compared with fed mice (P = 0.0009 and P = 0.0015). Fasted mice had higher viral loads (P = 0.0028) and impaired mCMV-specific interferon-gamma-producing CD8+ T cells (P = 0.0007), which improved with leptin rescue (P = 0.032). CONCLUSIONS: Undernutrition and its associated hypoleptinemia correlated with impaired allospecific and viral-specific immunities. Leptin administration decreased mCMV viral burden and increased mCMV-specific T-cell immunity, however, it did not increase rejection or worsen graft survival in complete major histocompatibility complex-mismatched skin allografts. Leptin may be a potential adjunctive therapy for CMV viremia in undernourished transplant recipients.

Full Text

Duke Authors

Cited Authors

  • David, E; Zhu, M; Bennett, BC; Cheng, D; Schroder, P; Nichols, A; Parker, W; Kirk, AD; MacIver, N; Chambers, ET

Published Date

  • December 1, 2021

Published In

Volume / Issue

  • 105 / 12

Start / End Page

  • 2554 - 2563

PubMed ID

  • 33724247

Electronic International Standard Serial Number (EISSN)

  • 1534-6080

Digital Object Identifier (DOI)

  • 10.1097/TP.0000000000003743

Language

  • eng

Conference Location

  • United States