CMV drives the expansion of highly functional memory T cells expressing NK-cell receptors in renal transplant recipients

Eur J Immunol. 2017 Aug;47(8):1324-1334. doi: 10.1002/eji.201747018. Epub 2017 Jul 3.

Abstract

Cytomegalovirus (CMV) is a common opportunistic infection encountered in renal transplant recipients (RTRs) and may be reactivated without symptoms at any time post-transplant. We describe how active and latent CMV affect T-cell subsets in RTRs who are stable on maintenance therapy. T-cell responses to CMV were assessed in RTRs (n = 54) >2 years post-transplant, and healthy controls (n = 38). Seven RTRs had CMV DNA detectable in plasma. CMV antibody and DNA aligned with increased proportions of CD8+ T cells and reduced CD4/CD8 ratios. This paralleled an expansion of effector memory T-cell (TEM ), terminally differentiated T-cell (TEMRA ) and CD57+ TEMRA cell populations. Expression of NK-cell receptors, LIR-1 and KLRG1 on CD4+ and CD8+ CD57+ TEM and TEMRA cells correlated with elevated interferon-γ and cytotoxic responses to anti-CD3 and increased cytotoxic responses to CMV phosphoprotein (pp) 65 in RTRs who carried CMV DNA. CD8+ T cells from all CMV seropositive RTRs responded efficiently to CMV immediate early (IE) -1 peptides. The data show that latent and active CMV infection can alter T-cell subsets in RTRs many years after transplantation, and up-regulate T-cell expression of NK-cell receptors. This may enhance effector responses of CD4+ and CD8+ T cells against CMV.

Keywords: Cytomegalovirus · NK-cell receptors · Renal transplantation · T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • CD4-CD8 Ratio
  • CD57 Antigens / genetics
  • CD57 Antigens / immunology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Cytomegalovirus / genetics
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / virology
  • DNA, Viral / blood
  • Female
  • Genes, Immediate-Early
  • Humans
  • Immunologic Memory*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Kidney Transplantation*
  • Killer Cells, Natural / immunology
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism*
  • Leukocyte Immunoglobulin-like Receptor B1
  • Male
  • Middle Aged
  • Peptides / pharmacology
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Receptors, Natural Killer Cell / genetics
  • Receptors, Natural Killer Cell / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transplant Recipients
  • Young Adult

Substances

  • Antigens, CD
  • CD57 Antigens
  • DNA, Viral
  • KLRG1 protein, human
  • LILRB1 protein, human
  • Lectins, C-Type
  • Leukocyte Immunoglobulin-like Receptor B1
  • Peptides
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • Trans-Activators
  • Interferon-gamma