Peripheral Blood CD38 Bright CD8+ Effector Memory T Cells Predict Acute Graft-versus-Host Disease

Biol Blood Marrow Transplant. 2015 Jul;21(7):1215-22. doi: 10.1016/j.bbmt.2015.04.010. Epub 2015 Apr 13.

Abstract

Acute graft-versus-host disease (aGVHD) is mediated by allogeneic T cell responses. We hypothesized that increases of peripheral blood-activated CD8+ effector memory T (TEM) cells would be observed after hematopoietic stem cell transplantation (HSCT) before onset of aGVHD symptoms. Blood was collected twice weekly after HSCT for 7 weeks in 49 consecutive pediatric and adult HSCT recipients. Samples were incubated with fluorochrome-conjugated antibodies against CD45, CD3, CD8, CD38, CD45RA, and CCR7 and analyzed using flow cytometry. TEM cells were defined as CD3+ CD8+ CCR7- CD45RA(-) lymphocytes. CD38 expression was used as a marker of T cell activation. Patients were followed for 100 days for development of aGVHD. Twenty-three patients developed grade 1 to 4 aGVHD at a median of 37 days (range, 15 to 79 days) after HCST. Absolute CD38 bright CD8+ TEM of > 35 cells/μL predicted aGVHD at a median of 8 days (range, 1 to 34) before aGVHD onset with a sensitivity of 82.6% and specificity of 91.6%. The cumulative incidence of aGVHD was 90% in patients with absolute CD38 bright CD8+ TEM >35 cells/μL and 15% in patients without (P < .0001). Quantification of CD38 bright CD8+ TEM cells may predict aGVHD in children and young adult HSCT recipients.

Keywords: CD38 bright CD8(+) effector memory T cells (TEMs); Effector memory T cells; Graft-versus-host disease (GVHD) predictive biomarker.

MeSH terms

  • ADP-ribosyl Cyclase 1 / genetics
  • ADP-ribosyl Cyclase 1 / immunology*
  • Acute Disease
  • Adolescent
  • Adult
  • Biomarkers / analysis
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Child
  • Child, Preschool
  • Common Variable Immunodeficiency / immunology
  • Common Variable Immunodeficiency / pathology
  • Common Variable Immunodeficiency / therapy*
  • Female
  • Gene Expression
  • Graft vs Host Disease / diagnosis*
  • Graft vs Host Disease / drug therapy
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / immunology
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / pathology
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Histocompatibility Testing
  • Humans
  • Immunologic Memory
  • Immunophenotyping
  • Immunosuppressive Agents / therapeutic use
  • Infant
  • Lymphocyte Activation
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Myeloablative Agonists / therapeutic use
  • Transplantation Conditioning*
  • Transplantation, Homologous

Substances

  • Biomarkers
  • Immunosuppressive Agents
  • Membrane Glycoproteins
  • Myeloablative Agonists
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1