In Vitro Activation of Cd8 Interphotoreceptor Retinoid-binding Protein-specific T Cells Requires Not Only Antigenic Stimulation but Also Exogenous Growth Factors.
From: Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, KY 40202, USA.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Apr 2006
- ISSN: 0022-1767
- Volume: 176
- Issue: 8
- Pages: 5006-14
- Medium: Print
- Language: English
- Citation (JAMA): Peng Yong, Shao Hui, Ke Yan, et al. In Vitro Activation of Cd8 Interphotoreceptor Retinoid-binding Protein-specific T Cells Requires Not Only Antigenic Stimulation but Also Exogenous Growth Factors.. J. Immunol. Apr 2006;176:5006-14
Abstract
In a previous study, we demonstrated that immunization with the uveitogenic peptide interphotoreceptor retinoid-binding protein (IRBP) 1-20 induces both CD4 and CD8 uveitogenic T cells in the B6 mouse. In the current study, we determined the role of the CD8 IRBP-specific T cells in the pathogenesis of experimental autoimmune uveitis. We also determined the conditions that facilitated the activation of CD8 autoreactive T cells. Our results showed that the beta2-microglobulin(-/-) mouse had a greatly decreased susceptibility to induction of experimental autoimmune uveitis by adoptive transfer of IRBP-specific T cells from B6 mice. We also showed that unlike CD4 autoreactive T cells, activated CD8 autoreactive T cells produced only a limited number and amounts of growth factors. As a result, in the absence of exogenously supplied growth factor(s), CD8 T cell activation and expansion were aborted. However, the growth and expansion of triggered CD8 autoreactive T cells could be supported by various cytokines. In addition to factors produced by activated CD4 autoreactive T cells, factors produced by nonlymphoid cells, such as IL-7 and IL-15, and unidentified factors in the culture supernatants of astrocytes and retinal pigment epithelial cells support the CD8 autoreactive T cells as well. Finally, we showed that, although several cytokines augmented the CD8 T cell response in vitro, different cytokines appeared to act on different CD8 subsets or on different activation/differentiation phases of CD8 autoreactive T cells. As a result, cytokines, such as IL-7, supported the proliferation and survival of CD8 IRBP-specific T cells, while others had only a growth-promoting effect.
Mesh Headings (Keywords): Adoptive Transfer, Animals, Autoimmune Diseases, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Proliferation, Cell Survival, Cytokines, Drug Synergism, Eye Proteins, Female, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, Retinol-Binding Proteins, Uveitis
Check for Full Text / PubMed Unique Identifier (PMID): 16585597
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