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Abstract: TH-OR57

Cytomegalovirus-Responsive CD4 T Cells Exhibit a Stable, Cytotoxic Phenotype During the First Year After Solid Organ Transplant

Session Information

Category: Transplantation

  • 2001 Transplantation: Basic

Authors

  • Ahmad, Ayah, Hunter College, New York, New York, United States
  • Higdon, Lauren, Stanford University, Stanford, California, United States
  • Maltzman, Jonathan S., Stanford University, Stanford, California, United States
Background

Cytomegalovirus (CMV) can cause serious disease in humans after solid organ transplant. In healthy individuals, immune surveillance typically controls primary infection of CMV. However, the latent virus remains dormant with the potential to reactivate periodically, causing deleterious effects on immune-compromised individuals. The anti-viral immune response to CMV in transplant recipients is hindered by associated immunosuppressive therapies. Antiviral CD4 T cells are an important component of viral control through production of inflammatory cytokines as well as lysis of infected cells. We sought to understand the homeostasis of this critical population in transplant recipients.

Methods

We characterized the phenotype and repertoire of protective CD4 T cells in six recipients of kidney or heart transplant within the first year after transplant. We analyzed peripherical blood samples from the recipients pre-, 3-, and 12-months post-transplant by both flow cytometry and targeted single cell sequencing. To analyze the phenotype of CMV-responsive CD4 T cells, we isolated CD4 T cells producing interferon gamma in response to CMV peptide stimulation and used targeted single cell RNA sequencing of T cells producing cytokine in response to CMV peptide stimulation to measure gene expression as well as T-cell receptors (TCR) to measure clonal expansion.

Results

By flow cytometry, we found that pre-transplant exposure to CMV was associated with elevated aging of CD4 T cells in comparison to recipients with no pre-transplant exposure. CD4 T cells maintained phenotypic stability over time. Our sequencing data also indicate that CMV-responsive CD4 T cells are largely anti-viral and cytotoxic, and phenotypically stable during the first year after transplant. We found that clonally expanded CMV-responsive CD4 T cells were primarily of an aged, cytotoxic phenotype as well.

Conclusion

Overall, these data indicate that in contrast to CD8 cells, transplantation and immunosuppression do not have a significant impact on CMV-responsive CD4 T cells within the first year post-transplant. Furthermore, the cytotoxic phenotype of the CD4 T cells suggests that these cells play an important role in control of CMV. Future studies are required to determine the impact of CMV-responsive CD4 T cells on control of CMV and post-transplant outcomes.

Funding

  • Other NIH Support