# EXPERIMENTAL AND CLINICAL ALLOGRAFT UNRESPONSIVENESS

> **NIH NIH R01** · NEW ENGLAND DEACONESS HOSPITAL · 1989 · $581,350

## Abstract

Chronic immunosupression in clinical transplantation is associated with
morbidity and mortality.  Induction of recipient unresponsiveness to donor
antigens would decrease requirements for immunosuppression and reduce
associated complications.  A model of specific unresponsiveness has been
developed in animals immunosuppressed with ALS and injected with donor bone
marrow that prolongs the survival of skin allografts in mice and renal
allografts in outbred dogs and rhesus monkeys.  Objectives of the present
application are (1) define the role of the histocompatibility complex in
the induction of unresponsiveness utilizing either donor marrow or specific
or nonspecific blood transfusions as antigen (2) characterize the cell(s)
in marrow responsible for unresponsiveness (3) isolate and characterize the
biological activity of suppressive factors in influencing unresponsiveness
(4) undertake a clinical trial of induction of unresponsiveness in
recipients of cadaveric or living-related transplants using ATG and donor
bone marrow (5) develop assays for early detection of rejection in
transplant patients.  The genetic influence on unresponsiveness will be
studied in congenic mice that differ at defined regions of the H-2
complex.  Mice will be given ALS and either donor marrow or donor specific
or nonspecific blood and immune reactivity will be studied by in vivo and
in vitro assays.  Cells contained in a marrow fraction shown to induce
unresponsiveness will be characterized by examining surface markers and by
their ability to respond in immune reactions.  Somatic cell hybridization
techniques will be used to obtain hybridoma cell lines of suppressor T
cells derived from ALS treated mice given blood transfusions.  Supernatants
from cell cultures will be assayed for suppressive activity.  Clinically,
the induction of unresponsiveness will be performed in patients receiving
either cadaver kidneys or living-related kidneys from one haplotype
mismatched, high MLC positive donors.  Patients will be followed serially
for helper/suppressor T cell ratios and lymphocyte responses to polyclonal
antigens and to donor specific and nonspecific antigens in an effort to
identify the state of specific unreponsiveness.  For the development of
assays for detection of rejection, immunoglobulins shed from renal tubules
and urinary CRP of transplant patients will be studied.  A sensitive
clinically applicable assay that will detect rejection before it is evident
clinically should improve treatment of rejection and prevent loss of grafts.

## Key facts

- **NIH application ID:** 3125792
- **Project number:** 5R01AI014551-13
- **Recipient organization:** NEW ENGLAND DEACONESS HOSPITAL
- **Principal Investigator:** Anthony P Monaco
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $581,350
- **Award type:** 5
- **Project period:** 1978-05-01 → 1992-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125792

## Citation

> US National Institutes of Health, RePORTER application 3125792, EXPERIMENTAL AND CLINICAL ALLOGRAFT UNRESPONSIVENESS (5R01AI014551-13). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125792. Licensed CC0.

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