Transfusion of blood products has been shown to impact a number of the recipient immune responses. The immunological consequences of transfusion include the production of alloantibodies, increased incidence of bacterial infection, increased relapse rates for at least some kinds of tumors, transfusion-associated graft-versus-host disease, increased survival of organ allografts, induction of anti-leukemic responses and reversal of some cases of spontaneous recurrent abortions. Although donor blood and recipient have been matched for blood group antigens, they are not routinely typed for HLA antigens. Thus in almost all cases, the transfusion results in the introduction of alloantigens to the recipients. The goal of the studies is to define the mechanisms regulating recipient immune responses to alloantigen in order to understand how transfusion can influence immune responses and how to best regulate these responses. One approach to study the recipient responses to alloantigen is to study the responses which are responsible for the elimination of the allogeneic donor cells. Recipient CD8+ and B cells are responsible for the elimination of allogeneic donor cells in a murine model sytem. Optimal responses by these cells requires help from CD4+ cells. The most rapid recipient responses were in response to activated donor CD4+ cells acting as alloantigen presenting cells. The proposed experiments will examine the relative importance of this novel pathway by comparing the role of donor CD4+ cells and macrophages as antigen presenting cells. These donor cell populations will be compared by measuring the minimum number of each type of donor cell that is required for recipient immune responses, the interactions that are important in activation of recipient effector responses for each type of cell and how the immune responses generated by these cells regulate other immune responses.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL059241-04
Application #
6537352
Study Section
Hematology Subcommittee 2 (HEM)
Program Officer
Barbosa, Luiz H
Project Start
1999-04-01
Project End
2003-03-31
Budget Start
2002-04-01
Budget End
2003-03-31
Support Year
4
Fiscal Year
2002
Total Cost
$204,515
Indirect Cost
Name
Rhode Island Hospital (Providence, RI)
Department
Type
DUNS #
161202122
City
Providence
State
RI
Country
United States
Zip Code
02903