The role of CD4 and CD8 T cells in the graft-versus-leukemia response in Rauscher murine leukemia.
Using a mouse model for MHC-matched unrelated donor transplantation, the relative influences of the CD4 and CD8 T cell subtypes on graft-versus-leukemia (GVL) were examined in a murine erythroleukemia induced in SJL/J mice by the injection of Rauscher virus. Following leukemia induction, the mice were given 9.5 Gy of total body irradiation (TBI) and injected with mixed marrow and spleen cells from normal MHC-matched--but minor histocompatibility mismatched--B10.S donors. Prior to their injection these donor cells were selectively depleted ex vivo for either CD4, CD8 or Thy-1 by exposure to the appropriate monoclonal antibody (MoAb) plus complement. Following transplant the recipients were observed for 20 weeks, along with parallel control groups, for survival, leukemia relapse, graft failure and graft-versus-host disease; 98% of the controls receiving no transplantation therapy died of leukemia. Among the controls that received TBI plus undepleted B10.S cells 30.9% died of leukemia relapse, but another 34.2% survived free of any clinical evidence of their leukemia. Donor cell depletion for Thy-1 increased the relapse to 68.8%, while survival fell to 10.4%. CD8 depletion resulted in a relapse of 55.6%, with a survival of 19.4%. By contrast, CD4 depletion had no effect on relapse, but did significantly increase the incidence of graft failure. At the end of the 20 weeks additional tests were run to determine whether those transplant survivors that had remained leukemia-free were also free of any residual Rauscher virus. Those tests showed that they were not.(ABSTRACT TRUNCATED AT 250 WORDS)
Cancer Research Laboratories, Allegheny-Singer Research Institute, Allegheny General Hospital, Pittsburgh, PA 15212.
J P
JP
OKunewick
D L
DL
Kociban
L L
LL
Machen
M J
MJ
Buffo
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology / Q000502:physiology; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D016827:CD8 Antigens / Q000502:physiology*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000503:physiopathology*; D006648:Histocompatibility / Q000276:immunology; D007942:Leukemia, Experimental / Q000382:microbiology / Q000503:physiopathology* / Q000628:therapy; D008562:Membrane Glycoproteins / Q000032:analysis / Q000276:immunology; D051379:Mice; D011925:Rauscher Virus / Q000302:isolation & purification / Q000502:physiology; D012074:Remission Induction; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000502:physiology; D018800:Thy-1 Antigens; D014019:Tissue Donors; D014916:Whole-Body Irradiation
D000954:Antigens, Surface; D016827:CD8 Antigens; D008562:Membrane Glycoproteins; D018800:Thy-1 Antigens