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Interleukin-12 can replace CD28-dependent T-cell costimulation during nonspecific cytotoxic T lymphocyte induction by anti-CD3 antibody.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Musgrave, Bruce L. Haeryfar, S. M. Mansour |
| Copyright Year | 2001 |
| Abstract | 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-gamma) 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-gamma. IL-2 is required for IL-12Rbeta2 expression by T cells activated in the presence of anti-CD86 mAb. Moreover, IL-12Rbeta2 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-12Rbeta2 induced by low levels of IL-2 synthesized by T cells activated in a CD28-independent manner. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jleukbio.org/content/69/1/113.full.pdf |
| PubMed reference number | 11200055v1 |
| Volume Number | 69 |
| Issue Number | 1 |
| Journal | Journal of leukocyte biology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | CD3 Antigens CD86 Antigen Cell Culture Techniques Cytotoxic T-Lymphocytes Granzymes Interferon Type II Interleukins Leukemia, B-Cell Ligands Monoclonal Antibodies Muromonab-CD3 T-Lymphocyte Transcription Initiation visilizumab |
| Content Type | Text |
| Resource Type | Article |
