# T CELL MAINTENANCE & THYMMIC ACTIVITY IN THE AGED

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 1993 · $165,072

## Abstract

DESCRIPTION (Adapted from applicants abstract):  Aging results in a
decline in immune vigor with the most significant changes occurring in
the T cell compartment.  It is frequently suggested that the diminution
in peripheral T cell activity is the result of thymic involution, a very
early event in the immunosenescence process, which is characterized by
the loss of lymphoid cells and the diminished emigration of mature T
cells to the periphery.  The first specific aim of the proposed
experimentation is to examine in depth the maturation of T cells in the
aged thymus.  Intrathymic T cell maturation is now recognized to be a
complex, multi-step process in which bone-marrow derived pro-thymocytes
seed the thymus.  Here the pro-thymocyte undergoes expansion and
sequential expression of Thy, T cell receptors, and the CD4 and CD8
markers.  It has previously been established that; aged bone marrow pro-
thymocytes are competent to seed a thymic rudiment, and that while the
aged thymus can accept pro-thymocytes, the aged thymus does not support
vigorous thymocyte proliferation.  It is hypothesized that specific steps
of intrathymic T cell differentiation are aging-"sensitive" occurring
with diminished efficiency in aged individuals, which ultimately results
in diminished T cell emigration.

Although there is a significant decline in naive T cell emigration from
the thymus with advancing age, the size of the peripheral T lymphocyte
compartment remains relatively constant.  This suggests that peripheral
expansion or self renewal play important roles in maintaining T cell
homeostasis.  The second specific aim is to examine these aspects of T
cell biology to determine how aging affects the lifespan of memory and
naive CD4+ and CD8+ T cells, the expansion potential of these subsets,
and their self-renewal capacity.  The ability to distinguish memory and
naive T cells on the basis of surface marker expression necessitates a
re-examination of older studies and may resolve conflicting data
regarding the "lifespan" of memory and naive cells in the aged animal.
It is anticipated that the results shall advance our understanding of the
consequences of aging on T cell differentiation and the peripheral T cell
compartment allowing the design of more effective means of manipulating
the immune system to achieve protective immunity in the aged population.

## Key facts

- **NIH application ID:** 3121881
- **Project number:** 5R01AG009948-02
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **SAM.gov UEI:** PHZJFZ32NKH4
- **Principal Investigator:** MARILYN L. THOMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $165,072
- **Award type:** 5
- **Project period:** 1991-09-30 → 1995-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121881

## Citation

> US National Institutes of Health, RePORTER application 3121881, T CELL MAINTENANCE & THYMMIC ACTIVITY IN THE AGED (5R01AG009948-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121881. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*