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Down‐Regulation of T‐Cell Proliferation in Response to Soluble Anti‐CD3 Antibodies through Development of Redirected Cytolytic Activity Eliminating Costimulatory Cells
Author(s) -
Lwin Tint,
Nakashima Izumi,
Nagase Fumihiko
Publication year - 1995
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.1995.tb02248.x
Subject(s) - cytolysis , biology , cd8 , cytotoxic t cell , t cell , microbiology and biotechnology , cd3 , antibody , antigen , antigen presenting cell , interleukin 21 , immunology , immune system , in vitro , biochemistry
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.