Cellular pathways for rejection of class-I-MHC--disparate skin and tumor allografts.
We have investigated the relative roles of the Lyt-2+ and L3T4+ T lymphocyte subsets in rejection of class-I-MHC-antigen-disparate skin and tumor allografts. To deplete T cells in vivo, rat anti-Lyt-2 or anti-L3T4 monoclonal antibodies (mAb) were administered to adult-thymectomized (ATX) recipient mice prior to transplantation. BALB/c (H-2d) recipient mice rejected the Ia- Sarcoma I (Sa1) (H-2a) tissue culture-derived tumor after depletion of the L3T4+ T cell subset in vivo. In contrast, depletion of the Lyt-2+ T cell subset permitted lethal tumor growth in all recipient mice. To determine the role of particular T cell subsets in rejection of Ld class-I-MHC-antigen-disparate allografts, BALB/c skin was transplanted to BALB/c-H-2dm2 recipient mice. Skin grafts were rejected by control mice with a mean survival time (MST) of 14.5 days. The MST of skin grafts for mice treated with anti-L3T4 mAb was 16.6 days. In contrast, administration of anti-Lyt-2 mAb alone (MST = greater than 47 days) or together with anti-L3T4 mAb (MST = greater than 50 days) caused prolonged or indefinite graft survival in all recipient mice. Depletion of specific T cell subsets was confirmed by flow cytometric analysis and by analysis of T cell function in vitro. These results suggest that Lyt-2+ T lymphocytes are essential for rejection of class-I-MHC-disparate allografts; indirect presentation of alloantigen to L3T4+ T cells may not be necessary for rejection.
Smith
D M
DM
Ben May Institute, University of Chicago, Illinois 60637.
Stuart
F P
FP
Wemhoff
G A
GA
Quintáns
J
J
Fitch
F W
FW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D006084:Graft Rejection; D006183:H-2 Antigens / Q000276:immunology*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008808:Mice, Inbred CBA / Q000276:immunology; D008819:Mice, Nude / Q000276:immunology; D009368:Neoplasm Transplantation; D010641:Phenotype; D012513:Sarcoma, Experimental / Q000276:immunology; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D006183:H-2 Antigens