# ANALYSIS OF NEONATAL H-2 TOLERANCE

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 1988 · $192,604

## Abstract

Over the past eight years, this laboratory has studied neonatal tolerance
induced to alloantigens encoded by genes within the murine major
histocompatibility complex, H-2.  During the past 2 1/2 years, we have
discovered that (a) clonal deletion of cytotoxic T cells specific for
tolerated antigens is incomplete in Class I-tolerant mice; (b) the tolerant
environment imposes specific unresponsiveness upon immunocompetent cells
directed at tolerated Class II alloantigens; and (c) specific
unresponsiveness is achieved in part by a suppression mechanism which is
donor I-J dependent.  In response to these findings we have reformulated
our original hypotheses concerning the induction and maintenance of
neonatal transplantation tolerances as follows:  Neonatal transplantation
tolerance is induced and maintained by two different, but complementary,
mechanisms:  (1) centrally-achieved clonal deletion/inactivation, resulting
in drastically reduced precursor cell frequencies compared to non-tolerant
animals (for Class I-recognizing cells, the process operates
pre-thymically, while for Class II-recognizing cells, the process operates
intrahymically); and (2) peripheral suppression that further reduces the
remaining Class II-recognizing activity to background, utilizing an I-J
dependent process.  To test these hypotheses, we propose the following
experimental approaches:  (1) Compare and contrast pre- and intrathymic
environments as sites at which clonal deletion/inactivation of developing T
cells with different functions can occur; (2) characterize the
tolerogen-specific T cells that are present within tolerant animals, using
in vitro cellular as well as molecular biological approahces, in an effort
to identify not only the site(s) at which clonal deletion operates, but to
understand its effect upon the T cell repertoire;  in addition, to extend
this analysis to the B lymphocyte compartment which also appears to contain
tolerogen-specific cells in tolerant mice; (3) employ assays of delayed
hypersensitivity to measure H-2 specific alloimmunity as an efficient
method for the study of the active suppression mechanism that down
regulates allo Ia-reactive T cells in Class II tolerant mice; and (4)
analyze the mechanisms by which donor I-J determinants dictate the
induction and maintenance of tolerance to Class II alloantigens.  The
results of these proposed experiments will promote our understanding of the
relative roles that clonal deletion and active suppression play in
tolerance of H-2 alloantigens, and by inference, in tolerance of self
antigens.

## Key facts

- **NIH application ID:** 3177859
- **Project number:** 5R01CA039078-05
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **SAM.gov UEI:** F8THLJQSAF93
- **Principal Investigator:** J WAYNE STREILEIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $192,604
- **Award type:** 5
- **Project period:** 1983-02-01 → 1989-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177859

## Citation

> US National Institutes of Health, RePORTER application 3177859, ANALYSIS OF NEONATAL H-2 TOLERANCE (5R01CA039078-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177859. Licensed CC0.

---

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