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| Content Provider | PubMed Central |
|---|---|
| Author | Inaba, Hiroto Steeves, Meredith Nguyen, Phuong Geiger, Terrence L. |
| Abstract | After stimulation, T-cells enter a transient refractory period, promoted by IL-2, during which they are resistant to re-stimulation. We previously demonstrated that these IL-2 and antigen stimulated refractory T-cells are able to suppress the antigen-induced proliferation of naïve T-cells in vitro. We show here that, after adoptive transfer, these T-cells are also able to suppress naïve T-cell proliferation in vivo. More interestingly, potently suppressive T-cells can be generated directly in vivo by stimulation with antigen and supplemental IL-2. The activity of the suppressive cells is dose-dependent, and the suppressor and suppressed T-cells need not be restricted to the same MHC or antigen. Similar to its role in promoting T-cell-mediated suppression in vitro, IL-2 is critical for the induction of suppressive activity in activated T-cells in vivo. Supplemental IL-2, however, cannot overcome the suppressive activity in target T-cells, indicating that suppression is not mediated by competition for this cytokine. Although the activated T-cells block naïve T-cell proliferation, the naive cells do engage antigen, and upregulate the CD25 and CD69 activation markers after stimulation. Therefore, activated T-cells stimulated in the presence of IL-2 develop MHC and antigen-unrestricted suppressive activity. These results provide a new mechanism for competition among CD4+ T-lymphocytes, in which initial waves of responding T-cells may inhibit subsequently recruited naïve T-cells. They further suggest a novel negative feedback loop limiting the expansion of immune responses that may be present during vigorous immune responses or after IL-2 immunotherapy. |
| Starting Page | 3323 |
| File Format | |
| ISSN | 15506606 |
| e-ISSN | 15506606 |
| Journal | Journal of immunology (Baltimore, Md. : 1950) |
| Issue Number | 5 |
| Volume Number | 181 |
| Language | English |
| Publisher Date | 2008-09-01 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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