The purpose of this study is to examine adoptive immunotherapy to induced B-cell neoplasia. Utilizing the agammaglobulinemic (A-gamma) chicken model developed in my laboratory, we will characterize suppressor T-cells induced in this model system and elucidate the suppression mechanism. An important aspect of this study will be to investigate the possibility that these suppressor T-cells may suppress not only normal B-cells but also lymphoma B-cells which are present in some avian leukoses. Suppressor cells specific for the inhibition of Ig production will be induced in A-gamma chickens (line 151/5 x 7/1) by injection of bursa cells. Suppressor cells will be characterized with respect to: 1) surface receptors, 2) adherence to nylon wool and lectins (Vicia villosa and Helix pomatia), 3) sensitivity to rabbit anti-chicken T-cells + C and radiation, and 4) other fractionation properties (density gradients on Percoll and rosetting technique). An in vitro assay for suppressor T-cells has been developed using either sheep RBC- or TNP-poly-acrylamide-primed spleen cells as targets. The mechanism of action of suppressor T-cells will be distinguished by whether they can suppress the Ig production of antigen-primed B-cells, inhibit the proliferation of mitogen-stimulation B-cells, or lyse B-cells. Suppressor T-cells obtained from spleens of bursa-immunized A-gamma chickens will be used in an attempt to suppress the growth of a B-cell leukosis line (LSCC-RP9) in vitro. The in vivo suppression of the growth of transplantable B-cell leukosis (LSCT-RP6) by suppressor T-cells will also be studied by directly transplanting LSCT-RP6 into A-gamma chickens. If the leukosis grows less in A-gamma than in normal chickens, it will indicated that the tumor may be susceptible to suppression. Further study of suppression of leukosis will be carried out by co-transfer of LSVT-RP6 cells and suppressor T-cells into normal chickens. Suppressor T-cells will also be used to treat B-cell leukosis-bearing chickens. The suppression of the growth of avian B-cell lymphomas by suppressor T-cells will potentiate a new approach for adoptive immunotherapy of B-cell neoplasms.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15CA043536-01
Application #
3437282
Study Section
Experimental Immunology Study Section (EI)
Project Start
1986-09-30
Project End
1989-09-29
Budget Start
1986-09-30
Budget End
1989-09-29
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
East Tennessee State University
Department
Type
Schools of Medicine
DUNS #
City
Johnson City
State
TN
Country
United States
Zip Code
37614