FACILITATING CELL INDUCED TOLERANCE IN ORGAN TRANSPLANTS
Project Number5R29AI040933-05
Contact PI/Project LeaderCOLSON, YOLONDA L
Awardee OrganizationDANA-FARBER CANCER INST
Description
Abstract Text
The major goal in organ transplantation is to prevent rejection yet
preserce recipient immunocompetence. Bone marrow (BM) chimerism,
resulting from engraftment of the donor BM stem cell (SC), is associated
with long-term donor-specific tolerance, associated with the infusion of
unmodified BM into ablated recipients has excluded the potential use of
chimerism in the induction of transplantation tolerance. The incidence
and severity of graft vs. host disease (GVHD) is directly related to the
antigenic disparity between the donor and the recipient. T-cell depletion
(TCD) of donor BM significantly reduces GVHD, but is associated with
a concurrent rise in the incidence of engraftment failure. Recently, we
have identified a rare BM-derived cell population, of unknown lineage,
which we call the facilitating cell (FC), that is sufficient to permit
engraftment of highly purified murine SC in completely MHC-disparate
recipients, without GVHD. The global aim in this proposal is to
characterize cell surface molecules on the FC population which are
responsible for the unique property of SC facilitation in vivo. The FC
is inadvertently removed by some techniques of TCD, because it does
express CD8alphabeta and CD3epsilon, however, it can be isolated in a
subpoplulation distinct from conventional T cells due to the absence of
the alpha beta or gamma delta T cell receptor (TCR) complex, CD3
expression without the conventional TCR heterodimers has been
described on immature thymocytes. In all cases, CD3epsilon was
associated with a TCR-surrogate or chaperone protein, in a functional
CD3 receptor complex. Therefore, we have focused our search for a
marker of FC function on the identification of CD3epsilon-associated
molecules (CD3AMs) on the FC cell surface. We have now identified
at least two CD3AMs on the FC, which are not found on conventional
T cells. In Aim I, we will Characterized the CD3AMs on the FC
Population: Is CD3AM Expression Independent of the T Cell Receptor?
CD3 expression in the absence of TCR heterodimers, suggest that the
FC is not a T cell, and therefore, the FC (and CD3AM expression)
should be present, and capable of SC facilitation, in mice deficient of T
cells. Therefore, in Aim II, we will Determine the Mechanistic Role of
CD3AMs on the Ability of the FC Population to Facilitate Engraftment
of the Allogeneic SC. Failure of a viable SC to engraft in an allogeneic
environment is likely to be secondary to the inability of the foreign
environment to foster SC differentiation and self-renewal. In Aim III,
we will Determine the Mechanism by Which The FC Facilitates SC
Survival: Are CD3AMs Necessary for SC Rescue?
National Institute of Allergy and Infectious Diseases
CFDA Code
855
DUNS Number
076580745
UEI
DPMGH9MG1X67
Project Start Date
01-April-1997
Project End Date
30-June-2003
Budget Start Date
01-July-2001
Budget End Date
30-June-2003
Project Funding Information for 2001
Total Funding
$116,114
Direct Costs
$70,000
Indirect Costs
$46,114
Year
Funding IC
FY Total Cost by IC
2001
National Institute of Allergy and Infectious Diseases
$116,114
Year
Funding IC
FY Total Cost by IC
Sub Projects
No Sub Projects information available for 5R29AI040933-05
Publications
Publications are associated with projects, but cannot be identified with any particular year of the project or fiscal year of funding. This is due to the continuous and cumulative nature of knowledge generation across the life of a project and the sometimes long and variable publishing timeline. Similarly, for multi-component projects, publications are associated with the parent core project and not with individual sub-projects.
No Publications available for 5R29AI040933-05
Patents
No Patents information available for 5R29AI040933-05
Outcomes
The Project Outcomes shown here are displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed are those of the PI and do not necessarily reflect the views of the National Institutes of Health. NIH has not endorsed the content below.
No Outcomes available for 5R29AI040933-05
Clinical Studies
No Clinical Studies information available for 5R29AI040933-05
News and More
Related News Releases
No news release information available for 5R29AI040933-05
History
No Historical information available for 5R29AI040933-05
Similar Projects
No Similar Projects information available for 5R29AI040933-05