Lymphokine enhances the expression and synthesis of Ia antigens on cultured mouse peritoneal macrophages.

Abstract

Soluble products from antigen stimulated Trypanosoma cruzi-immune spleen cells enhanced the expression of Ia antigens on proteose-peptone-elicited mouse peritoneal macrophages (M phi). Acquisition of Ia paralleled M phi activation, previously shown to be mediated by this same source of lymphokine (LK). Expression of Ia and four other plasma membrane antigens was monitored by quantitative binding and radioautographic studies with 125I-monoclonal antibodies. Immune LK selectively enhanced expression of Ia and, to a lesser extent, H-2D relative to control LK from antigen-stimulated noninfected spleen. The levels of three other non-major histocompatibility complex (MHC) antigens, including the trypsin-resistant Fc receptor, were similar in cells exposed to both sources of LK. As little as 1% immune LK induced one-half maximal expression of Ia. Kinetic studies revealed that much of the Ia on freshly explanted peritoneal M phi was lost during the 1st d of culture. In the continued presence of immune LK, Ia was re-expressed on virtually all M phi by the 2nd and 3rd d. Alternatively, > 95% Ia negative populations were obtained by culturing the cells 3 d; then, addition of LK induced Ia on most cells within 1 d. Once induced, Ia persisted on the M phi surface for at least 2 d. [35S]methionine radiolabeling indicated that immune LK selectively increased radiolabeling of M phi Ia, again with other non-MHC-linked plasma membrane polypeptides as controls. LK-induced Ia-bearing M phi were tested as primary mixed leukocyte reaction stimulators. 1 x 10(5)-2 x 10(5) M phi did not stimulate 4.5 x 10(6) responding T cells, whereas 10(4) dendritic cells induced strong responses, as previously described. Because Ia-positive M phi do not actively sensitize T cells in a model immune response, we propose that M phi MHC products serve primarily as recognition sites for previously sensitized T cells, thereby enhancing T cell-mediated M phi activation.

Interleukin 1 enhances T-dependent immune responses by amplifying the function of dendritic cells.

“…Note that the level of la on DC was not changed by IL-1 . The amount of la on DC was about twice that observed on macrophages exposed to IFN-'y, as was previously documented using binding of "I-1321-2 (22) . (B) Carbocyanine-dye labeling of DC .…”

“…Co ., Long Island, NY) for 3 d, with or without IFN-y at 10 U/ml . Elicited but not resident peritoneal cells responded to IFN-y as described (22). Induction of la antigens was visualized by staining cells with hybridoma culture supernatants (American Type Culture Collection, Bethesda, MD) : 10-2 .16 anti-la' (TIB 93) followed by FITC-goat anti-mouse Ig, B21-2 anti-la d followed by FITC-mouse anti-rat Ig, or biotin, 14-4-4S anti-I-E"' (HB 32) followed by FITC-avidin .…”

“…Induction of la antigens was visualized by staining cells with hybridoma culture supernatants (American Type Culture Collection, Bethesda, MD) : 10-2 .16 anti-la' (TIB 93) followed by FITC-goat anti-mouse Ig, B21-2 anti-la d followed by FITC-mouse anti-rat Ig, or biotin, 14-4-4S anti-I-E"' (HB 32) followed by FITC-avidin . Staining was monitored by immunofluorescence microscopy and judged to be specific through the use of an isotype-matched control mAb or with cells from the inappropriate haplotype (22) .…”

Surface properties of bacillus Calmette-Guérin-activated mouse macrophages. Reduced expression of mannose-specific endocytosis, Fc receptors, and antigen F4/80 accompanies induction of Ia.

“…Two hypotheses can be proposed to account for the changes in plasma membrane observed, viz., that the cell population is changed and represents an earlier stage or alternate pathway of macrophage differentiation or that the mature macrophage is able to modulate its surface phenotype. In this regard, it is known that Ia-like antigens may be expressed during earlier stages of myeloid differentiation (32), but that these antigens can also be induced on inflammatory peritoneal macrophages by treatment with lymphokines (11). It remains to be seen whether lymphokines can also induce the loss of F4/80 and other markers in nonactivated macrophages in vitro.…”

Is heterogeneous expression of HLA-DR antigens and CEA along with DNA-profile variations evidence of phenotypic instability and clonal proliferation in human large bowel carcinomas?

“…This epithelium is probably subjected to stimulae from the carcinoma and may express HLA-DR as a reactive sign like activated T-cells (Hammerling, 1976) and macrophages (Steinman et al, 1980). In graft-versus-host disease, colonic epithelium of the rat likewise expresses such antigens (Mason et al, 1981).…”