The immunomodulation of mylein basic protein-specific T helper cells by interleukin-2 / by Dana Jean Fraser.
| Author/creator | Fraser, Dana Jean author. |
| Other author | McConnell, Thomas J., degree supervisor. |
| Other author | East Carolina University. Department of Biology. |
| Format | Theses and dissertations |
| Production | 1995. |
| Description | 83 leaves, 3 leaves of plates : illustrations ; 28 cm |
| Supplemental Content | Access via ScholarShip |
| Subjects |
| Summary | Advisor: Thomas J. McConnell |
| Summary | The purpose of this thesis is to examine the regulation of interleukin-2 (IL-2) by myelin basic protein (MBP)-specific rat T cells, and to look at the effects of IL-2 on those same T cell lines. MBP-specific T cells have been implicated in Experimental Autoimmune Encephalomyelitis (EAE), an autoimmune disease which is inducible in many animal species including Lewis rats. EAE is studied as an animal model for multiple sclerosis because they are similar in etiology. This research focuses on IL-2 because it may play an important role in autoimmunity. Previously, the available source of rat IL-2 was the supernatant of Concanavalin A-activated rat splenocytes, which contains not only IL-2 but a number of other rat proteins including cytokines. To pursue this research, a source of rat IL-2 was needed which contained no other rat cytokines. The rat IL-2 gene was cloned, sequenced, and used to express the IL-2 protein in vitro in a baculovirus system. Through CTLL-2 bioassays and proliferative assays it was determined that the IL-2 protein was fully functional. Several aspects of the role of IL-2 in T cell regulation were examined using T cell proliferative assays and CTLL-2 bioassays. When MBP-specific T cells are reactivated within 4 days, they are refractory to IL-2 production. This refractory period may play a role in limiting the activation of autoreactive T cells. W3/25 is an anti-CD4 monoclonal antibody (mAb) that is inhibitory to T cell proliferation and lL-2 production. Even though W3/25 inhibited IL-2 production, proliferation, and rendered MBP-specific T cells anergic, IL-2 did not reverse the W3/25-mediated inhibition of proliferation. These results indicate that its effects are not just restricted to inhibition of IL-2 production, but may also involve inhibition of IL-2 receptor expression. When T cells were cultured in the absence of IL-2, they lost antigenic reactivity. T cells cultured in media supplemented with recombinant rat IL-2 were six-fold more responsive to antigen specific activation than T cells cultured in unsupplemented media. This loss of antigenic responsiveness in the absence of IL-2 may indicate yet another role for IL-2 in the maintenance of self-tolerance. Together these data contribute to the understanding of T cell regulation by IL-2. Increased knowledge of T cell regulation may provide insight to the origins of autoimmunity. |
| General note | Submitted to the faculty of the Department of Biology. |
| Dissertation note | M.S. East Carolina University 1995 |
| Bibliography note | Includes bibliographical references (leaves 79-83). |
| Genre/form | dissertations. |
| Genre/form | Academic theses. |
| Genre/form | Academic theses. |
| Genre/form | Thèses et écrits académiques. |
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