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Interleukin‐12 can replace CD28‐dependent T‐cell costimulation during nonspecific cytotoxic T lymphocyte induction by anti‐CD3 antibody
Author(s) -
Makrigiannis Andrew P.,
Musgrave Bruce L.,
Haeryfar S. M. Mansour,
Hoskin David W.
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.69.1.113
Subject(s) - cytotoxic t cell , cd86 , cd28 , ctl* , biology , cd80 , t cell , microbiology and biotechnology , il 2 receptor , immunology , immune system , cd40 , biochemistry , in vitro
Cytotoxic T lymphocyte (CTL) development is regulated closely by an intricate series of signals provided by the T‐cell receptor/CD3 complex, cytokines, and costimulatory ligand/receptor systems. In this study, we have explored the role of interleukin (IL)‐12 and CD28 in mouse CTL development. Activation of T cells with anti‐CD3 monoclonal antibody (mAb) in the presence of anti‐CD86 mAb, which prevents CD28‐CD86 interaction, led to decreased production of type 1 (IL‐2, interferon‐γ) and type 2 (IL‐4, IL‐6, IL‐10) cytokines, as well as diminished expression of granzyme B (Gzm B) and reduced cytotoxic effector function. Cytolytic activity in T‐cell cultures that were activated in the presence of anti‐CD86‐blocking mAb alone or in combination with anti‐CD80 mAb could be restored by the addition of exogenous IL‐12 at initiation of culture. The ability of IL‐12 to substitute for CD28‐costimulatory signaling during CTL development was found to be dependent on the presence of IL‐2 rather than interferon‐γ. IL‐2 is required for IL‐12Rβ2 expression by T cells activated in the presence of anti‐CD86 mAb. Moreover, IL‐12Rβ2 expression by T cells activated in the presence of anti‐CD86 mAb is enhanced by IL‐12. We, therefore, conclude that the ability of IL‐12 to substitute for CD28‐costimulatory signaling during CTL development is a result of the interaction of IL‐12 with IL‐12Rβ2 induced by low levels of IL‐2 synthesized by T cells activated in a CD28‐independent manner.