T-cell subsets, IFN-gamma production and efferent specificity in anti-parental tumor immunity induced by mouse sensitization with xenogenized variant cells.
In addition to previous evidence for a role of L3T4+ T cells in the protective anti-parental tumor immunity induced by xenogenized variant cells of a murine lymphoma (L5178Y/DTIC), we have investigated the possible participation in this effect of L5178Y tumor-specific lymphocytes of the Lyt-2+ T cell subset. Spleen cells from L5178Y/DTIC tumor-immunized mice produced high levels of IFN-gamma in vitro in response to parental antigens, and this activity was only abolished by treating the responder population with anti-Thy-1.2 antibody or a combination of anti-L3T4 and anti-Lyt-2.2 monoclonal antibodies (MAbs) plus complement. Positively selected L3T4+ and Lyt-2+ cells also produced IFN-gamma in vitro, provided accessory cells (plastic-adherent and Thy-1- Ia- splenocytes, respectively) were added to the lymphocyte-tumor cell cocultures. The production of IFN-gamma by purified L3T4+ and Lyt-2+ cells was inhibited by addition of the respective anti-class-II and anti-class-I H-2 antibody to the cultures. Administration of anti-IFN-gamma MAb in vivo significantly impaired the resistance of L5178Y/DTIC-immune mice to challenge with parental cells, as manifested by survival criteria and increased tumor-cell proliferation in the spleens of antibody-treated mice. Although anti-parental tumor protection in vivo and T-cell activation in vitro for IFN-gamma production were strictly antigen-specific, bystander tumor inhibition was observed when antigenically irrelevant cells were inoculated with the L5178Y lymphoma. These results suggest that both L3T4+ and Lyt-2+ T cells play a role in the protective anti-parental tumor immunity induced by xenogenized cells, and that their activity may involve IFN-gamma-mediated stimulation of non-specific tumoricidal mechanisms.
Bianchi
R
R
University of Perugia, Dept. of Experimental Medicine and Biochemical Sciences, Italy.
Fioretti
M C
MC
Romani
L
L
Grohmann
U
U
Cenci
E
E
Puccetti
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006183:H-2 Antigens / Q000009:adverse effects; D006649:Histocompatibility Antigens / Q000276:immunology; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008212:Lymphocyte Depletion; D008223:Lymphoma / Q000276:immunology*; D008297:Male; D051379:Mice; D013154:Spleen / Q000378:metabolism; D013160:Splenic Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism*; D014611:Vaccination
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D006183:H-2 Antigens; D006649:Histocompatibility Antigens; C029237:tumor-associated transplantation antigen; D007371:Interferon-gamma