Many potential mechanisms of graft rejection exist. Study of these mechanisms must take into account migratory patterns of sensitized cells; in the animal the graft alloantigen may be far removed from lymphoid depots and a particular cell can only exert an effect if it can get to the graft. Investigators of lymphocyte trafficking have had uncertain results as to whether trafficking is a specific or nonspecific phenomenon. The problems with these previous studies however include: (a) An assumption that only activated cells are those rapidly dividing i.e. those which take up radioactive label. (b) The effect of the label on the ability of cells to migrate. (c) Injection of labeled cells into the vascular compartment when in fact they may not normally have access. These studies have shown that lymphocyte migration depends on (1) the subpopulation to which the lymphocyte belongs, (2) the state of activation of the lymphocyte, and (3) the host immune state. We propose to utilize the limiting dilution assay technique to study the distribution of sensitized proliferating and precytotoxic/cytotoxic cells throughout the sponge allograft sensitized mouse. Using these functional assessments of lymphocytes rather than radiolabel eliminates the need to introduce radiolabeled cells into the intravascular space. The use of the sponge allograft model in the mouse allows for easy access to all compartments including the cells infiltrating the allograft.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R23)
Project #
5R23AI021560-03
Application #
3445584
Study Section
Immunobiology Study Section (IMB)
Project Start
1984-07-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Ascher, N L; Clemmings, S M; Cahill, D R et al. (1988) Lymphocyte traffic and distribution after sponge matrix allograft using limiting dilution analysis. Transplant Proc 20:231-2
Ascher, N L (1987) Effector mechanisms in allograft rejection. Transplant Proc 19:57-60
Clemmings, S M; Hoffman, R A; Cahill, D R et al. (1987) Compartmentalization and lymphocyte traffic after allograft challenge. Transplant Proc 19:359-60
Cahill, D R; Hoffman, R A; Clemmings, S M et al. (1987) Cloned T cells do not require host H-2 restrictions to elicit delayed-type hypersensitivity. Transplant Proc 19:410-1
Ascher, N L; Cahill, D R; Hoffman, R A et al. (1986) Lymphocytes capable of mediating delayed-type hypersensitivity reactions accumulate within sponge matrix allografts. Surgery 100:321-8