Down-Regulation of T-Cell Proliferation in Response to Soluble Anti-CD3 Antibodies through Development of Redirected Cytolytic Activity Eliminating Costimulatory Cells

• Published in: MICROBIOLOGY and IMMUNOLOGY 1995, Vol.39(8), pp.599-606
• Main Authors: Lwin, Tint, Nakashima, Izumi, Nagase, Fumihiko
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Animals; Anti-CD3 redirected cytolysis; Antibodies - immunology; Biological and medical sciences; CD3 Complex - immunology; CD8+ T cells; CD8-Positive T-Lymphocytes - immunology; Cell Division - drug effects; Cells, Cultured; Cytotoxicity, Immunologic; Down-Regulation; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Mice; Mice, Inbred BALB C; Modulation of the immune response (stimulation, suppression); T-cell proliferation; T-Lymphocytes - immunology
• ISSN: 0385-5600; 1348-0421
• DOI: 10.1111/j.1348-0421.1995.tb02248.x

CD4+ T-depleted spleen cells (CD8+ T cells) activated by anti-CD3 antibodies (aCD3) suppressed proliferation of CD8+ T-depleted spleen cells (CD4+ T cells) and fresh normal T cells in response to aCD3. Antigen-nonspecific cytolytic activity was induced in splenic CD8+ T cells by stimulation with aCD3 and showed the peak level on day 3, whereas cytolytic activity induced in CD4+ T cells was weak. Intact Ig but not F(ab')2 of aCD3 induced and mediated cytolytic activity. Correspondingly, the cytolytic activity induced by aCD3 was directed against target cells bearing Ig-binding Fc-receptor activity and cytolysis was inhibited by the addition of free Ig into the assay system. We showed that aCD3-activated T cells carried a high level of aCD3 on their surface at the time after the peak proliferation when they attained high cytolytic activity. This raised the possibility that the anti-CD3-induced aCD3-redirected cytolytic activity eliminated Fc-receptor-bearing costimulatory cells in the culture for down-regulation of the T-cell proliferation. This view was supported by partial restoration of anti-CD3-induced low responsiveness of CD8+ T cells by the addition of fresh costimulatory cells. These results suggested a new pathway of down-regulation of T-cell proliferation by aCD3-activated cytolytic CD8+ T cells.