# T CELL ABNORMALITIES IN AUTOIMMUNE 1PR/1PR MICE

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 1992 · $57,497

## Abstract

DESCRIPTION (Adapted from the applicant's abstract):  MRL/Mp-lpr/lpr mice
develop a systemic lupus erythematosus (SLE) like disease similar to human
SLE and develop an age dependent lymphoproliferative disease characterized
by massive accumulation of an abnormal subset of T lymphocytes.  The
abnormal lpr T cells are unresponsive to many mitogenic stimuli.
Phenotypically normal CD4+ T cells, which account for only 5 to 10 percent
of the lymphocytes in lpr mice, also play an important role in the
pathogenesis of autoimmune disease.  These CD4 bearing cells may recognize
self Ia antigens or some processed self peptides bound to Ia. Interaction
of these autoreactive T cells with B cells may result in production of
autoantibodies.  T cells and self-antigens may, therefore, be the cause of
autoimmune diseases in these mice.  T cell hybridomas were generated by
fusing CD4+ lpr T cells with BW5147.  These hybridomas will be used to
investigate the T cell receptor repertoire of the autoreactive T cells.  T
cell hybridomas or their supernatants will be cultured with B cells to
determine if they can activate B cells to produce antibodies.  The isotype
and specificities of antibodies produced will be determined.  B cells from
lpr mice may possess some intrinsic features which render them more
stimulatory in activating autoreactive T cells.  While it is clear that
CD4+ T cells are essential for the development of lymphoproliferation in
lpr mice, the relationship between CD4+ T cells and abnormal T cells is not
clear.  CD4+ T cells may be the precursors of the abnormal T cells.
Lymphocytes infiltrate the kidneys and salivary glands in lpr mice.  The
majority of the infiltrating lymphocytes are CD4+ T cells.  T cell clones
and T cell hybridomas will be generated from infiltrating lymphocytes
obtained from the kidneys and salivary glands of lpr mice.  The T cell
receptor (TCR) repertoire of these T cell clones and hybridomas will be
characterized.  Antigen presenting cells in the kidneys and salivary glands
of lpr mice will also be isolated and their ability to activate the T cell
clones or hybridomas will be determined.  These studies should provide new
insights into the relationship between autoreactive T cells, abnormal T
cells and lymphocytes infiltrating inflamed organs in lpr mice.

## Key facts

- **NIH application ID:** 3158379
- **Project number:** 5R01AR038018-06
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **SAM.gov UEI:** FLJ7DQKLL226
- **Principal Investigator:** MAN-SUN M SY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $57,497
- **Award type:** 5
- **Project period:** 1988-10-01 → 1993-01-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158379

## Citation

> US National Institutes of Health, RePORTER application 3158379, T CELL ABNORMALITIES IN AUTOIMMUNE 1PR/1PR MICE (5R01AR038018-06). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3158379. Licensed CC0.

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