Tetramers reveal CD4+ T cells that are specific for U1-70 in systemic lupus erythematosus
Abstract/Contents
- Abstract
- Antigen-specific CD4+ T cells have been implicated in the autoimmune disease systemic lupus erythematosus (SLE), yet little is known about the function of these T cells or the precise peptide antigens that they recognize. We hypothesized that antigen-specific CD4+ T cells contribute to lupus pathology through two mechanisms: (1) by providing help to B cells for pathogenic autoantibody production, and (2) by directly promoting inflammation through the secretion of proinflammatory cytokines. We tested these two hypotheses by generating a series of MHC class II tetramers of I-Ek containing peptides from the spliceosomal protein U1-70. These tetramers specifically stained distinct CD4+ T cell populations in MRL/lpr mice. Using these reagents, we demonstrated that CD4+ T cells specific for U1-70 (131-150):I-Ek correlated with disease and with anti-U1-70 autoantibody production, expressed ROR[lowercase gamma]t and Tbet, and produced IFN[lowercase gamma] and IL-17A in an I-Ek-dependent manner. We confirmed our findings from mice in human patients with SLE and mixed connective tissue disease (MCTD). U1-70 specific CD4+ T cells obtained from peripheral blood mononuclear cells (PBMCs) of patients with SLE produced IFN[lowercase gamma] in all 5 patients tested and IL-17A in 1 out of 2 patients whose serum contained RNP autoantibodies. These data support the hypotheses that antigen-specific T cells recognize the same autoantigens as B cells, and that they produce proinflammatory cytokines. These studies represent the first reported tetramers for studying antigen-specific T cells in a mouse model of lupus, and demonstrate an antigen-specific source of IL-17A in human autoimmune disease.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2010 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Kattah, Nicole Hanick |
|---|---|
| Associated with | Stanford University, Department of Immunology. |
| Primary advisor | Utz, Paul |
| Thesis advisor | Utz, Paul |
| Thesis advisor | Davis, Mark M |
| Thesis advisor | Robinson, William (William Hewitt) |
| Thesis advisor | Steinman, Lawrence |
| Advisor | Davis, Mark M |
| Advisor | Robinson, William (William Hewitt) |
| Advisor | Steinman, Lawrence |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Nicole Hanick Kattah. |
|---|---|
| Note | Submitted to the Department of Immunology. |
| Thesis | Ph.D. Stanford University 2010 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2010 by Nicole Hanick Kattah
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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