Changes in splenic macrophage Mac antigen expression during tumor growth: a kinetic study of accessory cell function and antigen-defined phenotypes.
Three monoclonal antibodies, anti-Mac-1, -2, and -3, were used to modify accessory cell activity of whole spleen cell (WSC) or splenic adherent cell (SAC) preparations from normal or tumor-bearing hosts (TBH). Ligand activation by anti-Mac-1, -2 and -3 modified normal and TBH WSC lectin responses differentially; the most pronounced effect was with anti-Mac 1, which augmented normal WSC responsiveness, whereas anti-Mac-2 and -3 augmented TBH WSC mitogenesis. Ligand interaction with Mac-2 epitopes resulted in significantly suppressed normal host WSC responsiveness. With complement, anti-Mac-1 and -3 each reduced normal and TBH WSC proliferation. Reconstitution of blastogenesis was obtained by combining Mac-2-depleted with Mac-3-depleted normal host WSC or by combining Mac-1-depleted with Mac-2-depleted TBH WSC. To evaluate the role of different types of splenic adherent cells in T cell lectin responsiveness, adherent cells were collected and depleted by antibody plus complement treatment and added back to normal T cells. Removal of TBH SAC indicated the number of Mac-1+ SAC susceptible to lysis increased during tumor growth, whereas those susceptible to anti-Mac-2 and -3 treatment decreased. Removal of Mac-1+ normal host SAC stimulated the supportive accessory function of the remaining SAC. Enhancing accessory cell function diminished after removal of Mac-2+ or Mac-1+ normal and TBH SAC, respectively. T cell responsiveness was increased by adding back combinations of normal host SAC, Mac-1-depleted with Mac-3-depleted SAC or Mac-1-depleted with Mac-2-depleted SAC but not by Mac-2-depleted with Mac-3-depleted SAC. In contrast, none of the TBH SAC combinations were completely restored in accessory activity. In summary, SAC from normal host demonstrated an accessory cell function corresponding to a Mac-1- phenotype, which was either replaced or obscured by the predominance of a Mac-1+ phenotype in TBH.
D000818:Animals; D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D003208:Concanavalin A / Q000276:immunology; D007111:Immunity, Cellular; D008213:Lymphocyte Activation; D016177:Macrophage-1 Antigen; D008264:Macrophages / Q000145:classification / Q000276:immunology*; D051379:Mice; D012513:Sarcoma, Experimental / Q000276:immunology*; D013154:Spleen / Q000276:immunology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D016177:Macrophage-1 Antigen; D003208:Concanavalin A