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

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 aCD...

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Bibliographic Details
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
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Summary: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.
ISSN:0385-5600
1348-0421
DOI:10.1111/j.1348-0421.1995.tb02248.x