The immunological mouse mutants nude (nu) and rhino (hrrh) generate cytotoxic effector cells following adoptive immunotherapy but fail to reject a transplanted tumor.
Adoptive immunotherapy, consisting of cyclophosphamide injection and the i.v. transfer of tumor-sensitized T cells, resulted in rejection of the immunogenic fibrosarcoma, MCA/76-9, by syngeneic C57BL/6J (B6) mice. The same treatment of tumor-bearing congenic immunodeficient mice, homozygous for the deleterious mutations nude (nu) and rhino (hrrh), did not result in tumor rejection. Paradoxically, the intratumor and intrasplenic changes taking place in each of the three strains after therapy were indistinguishable. There was an increase in Thy-1+, Ly-2+, or L3T4+ cells at the tumor site 8 days after adoptive immunotherapy and a similar increase in Thy-1+ cells in the spleen. Moreover, the T cells isolated from the tumors or spleens from each genotype were shown to be specifically cytotoxic in vitro as well as in an in vivo Winn assay. Further evidence that immune amplification had occurred in the immunological mutant mice was provided by experiments showing (a) the ability of spleen cells from tumor-bearers and those tested after therapy to produce IL-2 in response to Con A stimulation and (b) an increase in class II-MHC antigen expression by tumor-associated macrophages. The data suggest that, although amplification of antitumor immune responses occurred in the immunological mutants, the absence of a critical host factor limited the potency of the antitumor response.
Evans
R
R
Jackson Laboratory, Bar Harbor, Maine 04609.
Duffy
T M
TM
Shultz
L D
LD
D000818:Animals; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D005354:Fibrosarcoma / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D006084:Graft Rejection; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007116:Immunization, Passive; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL / Q000276:immunology; D008817:Mice, Mutant Strains / Q000276:immunology*; D008819:Mice, Nude / Q000276:immunology*; D009368:Neoplasm Transplantation; D013154:Spleen / Q000637:transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation
D000949:Histocompatibility Antigens Class II; D003520:Cyclophosphamide