# Immune control of chronic viral infection in solid organ transplantation

> **NIH VA I01** · VETERANS ADMIN PALO ALTO HEALTH CARE SYS · 2023 · —

## Abstract

Immunosuppression required for lifesaving solid organ transplantation induces significant
morbidity including increased recurrence of latent viral infection in transplant recipients.
Approximately 60-70% of adults in the United States are latently infected with
Cytomegalovirus (CMV). Control of latent CMV is thought to depend on a constantly active
immune response, specifically by memory T lymphocytes. In those with a normal immune
system, control of latent CMV is a constant “battle” and results in so called memory inflation.
In aged individuals, CMV responsive cells may constitute upward of 50% of the total CD8 T
cell population. Despite active monitoring and anti-viral prophylaxis, immunosuppressed
transplant recipients have a 10-15% incidence of recurrent CMV manifesting either as
isolated viremia or may include end-organ damage. To better understand the immune
response to CMV in solid organ transplant recipients, we have previously used multi-
parameter flow cytometry to characterize CMV-responsive CD8+ T cells from pre-transplant
to one year post transplant in a cohort of heart or kidney transplant recipients. Strikingly,
despite a lack of clinical evidence for CMV reactivation, CMV-responsive CD8 T cells
increased from approximately 4% to 12% of the CD8 repertoire during the first year post-
transplant. Preliminary data indicates that the expansion maintains clonal competition and
suggests intraclonal heterogeneity of function that changes with time. These data lead us to
the hypothesis that immunosuppression induces oligoclonal expansion of CMV-
responsive T cells resulting in accelerated inflation and premature immune
senescence. To address this hypothesis, we have initiated collaborations with Mark Davis,
Jorg Goronzy and Purvesh Khatri at Stanford University. Subjects will be recruited from the
Portland, Nashville, Pittsburgh and Palo Alto VA transplant centers. We will use innovative
approaches involving cutting edge cytometry and single cell analysis . Specifically we
propose the following aims: Aim1, Determine if transplantation and immunosuppression
induced expansion alters the T cell repertoire and function and Aim 2, Determine if
immunosuppression in the setting of organ transplantation leads to pre-mature aging of the
CMV-responsive population and decreased functional responses. The results of these
studies will give us new fundamental insight into the biology of CMV-responsive T cells and
can be used to develop new therapies that will extend the lives of veterans.

## Key facts

- **NIH application ID:** 10595487
- **Project number:** 5I01CX001971-04
- **Recipient organization:** VETERANS ADMIN PALO ALTO HEALTH CARE SYS
- **Principal Investigator:** JONATHAN S MALTZMAN
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-10-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10595487

## Citation

> US National Institutes of Health, RePORTER application 10595487, Immune control of chronic viral infection in solid organ transplantation (5I01CX001971-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10595487. Licensed CC0.

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