Dynamics of cell-mediated immune responses to cytomegalovirus in pediatric transplantation recipients

Manisha Patel1, Martha Stefanidou, Caroline B Long

  • 1Albert Einstein College of Medicine, Children's Hospital at Montefiore, Bronx, NY, USA.

Insights

Monitoring cellular immune responses (CMI) alongside cytomegalovirus (CMV) DNA levels in pediatric transplant recipients can help predict invasive CMV disease. CMI responses decrease post-transplant but recover, aiding in predicting disease progression.

Area of Science:

  • Immunology
  • Transplantation Science
  • Virology

Background:

  • Cytomegalovirus (CMV) infection is a significant risk in pediatric transplantation.
  • Cellular immune monitoring (CMI) combined with CMV DNA quantification (DNAemia) may identify at-risk recipients.
  • Understanding CMI dynamics post-transplant is crucial for managing CMV disease.

Purpose of the Study:

  • To assess the feasibility of monitoring CMI in pediatric transplantation candidates.
  • To correlate CMI responses with CMV DNAemia and predict CMV disease progression.
  • To characterize CMI patterns in relation to CMV exposure and transplant status.

Main Methods:

  • Collected peripheral blood mononuclear cells (PBMC) from pediatric transplant candidates and long-term transplant (LTTx) patients.
  • Stimulated cells with anti-CD3 monoclonal antibody (mAb) or CMV pp65 peptide pools.
  • Assessed interferon-gamma (IFNG) responses using enzyme-linked immunosorbent spot (ELISpot) assay and measured cytokine secretion.

Main Results:

  • IFNG responses to anti-CD3mAb were lower pre-transplant and at 1-3 months post-transplant, recovering by 6 months.
  • CMV-seropositive recipients showed similar CMI patterns, with recovery to pp65 stimulation by 3 months.
  • Three LTTx subjects with CMV DNAemia showed transiently decreased CMI responses that resolved with DNAemia.

Conclusions:

  • Monitoring CMI in pediatric transplant recipients is feasible.
  • CMI monitoring can serve as an adjunct biomarker for predicting CMV progression and recovery.
  • CMI dynamics reflect the immune status and response to CMV in transplant patients.