# T CELL DEVELOPMENT IN THE THYMUS

> **NIH NIH R01** · WALTER AND ELIZA HALL INST MEDICAL RES · 1987 · $74,188

## Abstract

The influence of the thymus on the immune defense system will be studied
using a quantitative balance-sheet approach to the intrathymic pathways of
T cell development.  The investigation will use both the intact mouse
thymus, and culture models of the intra-thymic environment consisting of
lymphoid elements incubated on monolayers of epithelial and other
non-lymphoid cells.  Thymocyte subsets from the cortex and the medulla will
be isolated on the basis of surface markers using a range of monoclonal
reagents and fluorescence activated cell sorting.  The earliest cells of
the pathway, intrathymic stem cells and precursor cells, will be separated
from the blast population on the basis of markers, thymus reconstitution
potential and generative ability in vitro.  Factors controlling the arrival
of new stem cells into the adult thymus will be determined.  The cells at
the end of the pathway, the immediate post-thymus migrants, will be
isolated from the spleen or lymph nodes by cell sorting on the basis of
surface fluorescence a few hours after intrathymic labeling.
Precursor-product relationships between thymocyte subsets will be
established by using surface markers, by using localized application of
isotopically labeled DNA precursors and surface fluorescein tracers, and by
using short-term culture.  The basis for the lack of function in cortical
thymocytes will be explored using a variety of stimuli which might lead to
activation.  Their interaction with epithelial components via surface
protein or carbohydrate determinants will be investigated.  The total
functional potential of the thymocyte subset will be assessed in a
cell-by-cell way using new, high cloning efficiency limit-dilution
microculture systems, with either a lectin-mediated non-specific readout,
or with a specific readout to measure the frequency of cytotoxic precursors
of a given H-2 restriction pattern.  The latter approach will require
development of culture conditions which maintain precise immunological
specificity, and the basis of cytotoxic T cell specificity degradation will
be explored.  Possible changes in H-2 restriction repertoire during
intrathymic development, from the earliest to the latest cells in the
sequence, will be followed.  Culture of isolated subjects of early
thymocytes on non-lymphoid monolayers differing in H-2 status will be used
in an attempt to mimic any thymus influence on the H-2 restriction
repertoire.

## Key facts

- **NIH application ID:** 3127130
- **Project number:** 2R01AI017310-07
- **Recipient organization:** WALTER AND ELIZA HALL INST MEDICAL RES
- **SAM.gov UEI:** ZVG2YKNTQPB9
- **Principal Investigator:** KEN D SHORTMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $74,188
- **Award type:** 2
- **Project period:** 1987-05-01 → 1990-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127130

## Citation

> US National Institutes of Health, RePORTER application 3127130, T CELL DEVELOPMENT IN THE THYMUS (2R01AI017310-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127130. Licensed CC0.

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