Graft-versus-Leukemia, Donor Selection for Adoptive Immunotherapy in Mice
During the past several years, evidence has accumulated indicating that functionally separate subpopulations of T-lymphocytes are present in various mammalian species; these include suppressor (16), helper (10), and effector (11) T-cells. We recently repo
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239 S. J. Baum et al. (eds.), Experimental Hematology Today © Springer Science+Business Media New York 1977
Graft-versus-Leukemia, Donor Selection for Adoptive Immunotherapy in Mice William P. LeFeber, Robert L. Truitt, William C. Rose, and Mortimer M. Bertin
Experimental Models of Clinical Conditions in Hematology patibility complex and at minor histocompatibility loci; (2) unprimed congenic mice mismatched with AKR only at a portion of the H-2 complex; (3) unprimed H-2 matched mice; and (4) H-2 matched mice primed with multiple injections of irradiated spleen cells from leukemic AKR mice. As tested in these experiments, mice of the H-2 mismatched SJL strain appeared to be most suitable for their high GvL reactivity and minimal acute GvH reactivity. All other tested strains were less desirable because of lower GvL reactivity higher GvH reactivity, or both.
years has been maintained in our laboratory as an acute lymphoblastic leukemia by weekly i.v. passage. Leukemia cells were obtained from the spleens of AKR mice that had received 2.5 x 1 100
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•Gvl reactivity of transplanted immunocompetent cells was evaluated in immunosuppressed leukemic AKR mice by means of a bioassay. Survival studies were used to evaluate GVH reactivity of the cells in immunosuppressed nonleukemic AKR mice. hMeasured by bioassay of primary recipient's spleen; values are for secondary recipients. •Measured in primary recipients. •No secondary recipients died after day 44. •Data from ref. 4 (using a different bioassay model) have been included for comparison.
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Experimental Models of Clinical Conditions in Hematology
the five remaining strains (groups 5-9) in comparison with groups 1-4 (p < 0.01). Cells from DBA/2 donors (group 7) had moderate GvL reactivity, as evidenced by 70% (21130) survival ofthe secondary recipients, but this was significantly less (p < 0.05) than that exhibited by mice of the DBA/I and SJL strains (groups 5 and 9). Immunocompetent cells from DBA/I and SJL donors eliminated all viable leukemic cells from the spleens of the primary recipients with resultant survival of all secondary recipients. GvH ASSAYS USING UNPRIMED DONORS
Also summarized in Table I are the results of the GvH assays. The doses of 400 R TBI and 185 mg/kg Cytoxan administered to nonleukemic 8- to 10-week-old AKR mice as immunosuppressive conditioning for the GvH assays were toxic and resulted in an MST of 48 days with 39% 100-day survival (group I, Table 1). The chemoradiotherapy toxicity could be overcome (p < 0.01) by transplanting syngeneic bone marrow and lymph node cells (cf. groups I and 2). Cells from H-2 identical ST/b (group 3) and congenic AKR.M (group 4) mice caused minimal acute GvH disease [10% (3/30) and 3% (1130) deaths before day 30] and moderately severe delayed GvH disease. Cells from DBA/I donors (group 5) caused the most severe GvH disease of all donor strains (p < 0.01) with a 7-day MST and death of all recipi
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