High frequency of cytolytic 21-hydroxylase-specific CD8+ T cells in autoimmune Addison's disease patients.
The mechanisms behind destruction of the adrenal glands in autoimmune Addison's disease remain unclear. Autoantibodies against steroid 21-hydroxylase, an intracellular key enzyme of the adrenal cortex, are found in >90% of patients, but these autoantibodies are not thought to mediate the...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Association of Immunologists
2014
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| _version_ | 1797088843316330496 |
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| author | Dawoodji, A Chen, J Shepherd, D Dalin, F Tarlton, A Alimohammadi, M Penna-Martinez, M Meyer, G Mitchell, A Gan, E Bratland, E Bensing, S Husebye, E Pearce, S Badenhoop, K Kämpe, O Cerundolo, V |
| author_facet | Dawoodji, A Chen, J Shepherd, D Dalin, F Tarlton, A Alimohammadi, M Penna-Martinez, M Meyer, G Mitchell, A Gan, E Bratland, E Bensing, S Husebye, E Pearce, S Badenhoop, K Kämpe, O Cerundolo, V |
| author_sort | Dawoodji, A |
| collection | OXFORD |
| description | The mechanisms behind destruction of the adrenal glands in autoimmune Addison's disease remain unclear. Autoantibodies against steroid 21-hydroxylase, an intracellular key enzyme of the adrenal cortex, are found in >90% of patients, but these autoantibodies are not thought to mediate the disease. In this article, we demonstrate highly frequent 21-hydroxylase-specific T cells detectable in 20 patients with Addison's disease. Using overlapping 18-aa peptides spanning the full length of 21-hydroxylase, we identified immunodominant CD8(+) and CD4(+) T cell responses in a large proportion of Addison's patients both ex vivo and after in vitro culture of PBLs ≤20 y after diagnosis. In a large proportion of patients, CD8(+) and CD4(+) 21-hydroxylase-specific T cells were very abundant and detectable in ex vivo assays. HLA class I tetramer-guided isolation of 21-hydroxylase-specific CD8(+) T cells showed their ability to lyse 21-hydroxylase-positive target cells, consistent with a potential mechanism for disease pathogenesis. These data indicate that strong CTL responses to 21-hydroxylase often occur in vivo, and that reactive CTLs have substantial proliferative and cytolytic potential. These results have implications for earlier diagnosis of adrenal failure and ultimately a potential target for therapeutic intervention and induction of immunity against adrenal cortex cancer. |
| first_indexed | 2024-03-07T02:55:54Z |
| format | Journal article |
| id | oxford-uuid:af4b3aaf-fd26-4e95-a17b-8ec50456cde5 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:55:54Z |
| publishDate | 2014 |
| publisher | American Association of Immunologists |
| record_format | dspace |
| spelling | oxford-uuid:af4b3aaf-fd26-4e95-a17b-8ec50456cde52022-03-27T03:48:30ZHigh frequency of cytolytic 21-hydroxylase-specific CD8+ T cells in autoimmune Addison's disease patients.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:af4b3aaf-fd26-4e95-a17b-8ec50456cde5EnglishSymplectic Elements at OxfordAmerican Association of Immunologists2014Dawoodji, AChen, JShepherd, DDalin, FTarlton, AAlimohammadi, MPenna-Martinez, MMeyer, GMitchell, AGan, EBratland, EBensing, SHusebye, EPearce, SBadenhoop, KKämpe, OCerundolo, VThe mechanisms behind destruction of the adrenal glands in autoimmune Addison's disease remain unclear. Autoantibodies against steroid 21-hydroxylase, an intracellular key enzyme of the adrenal cortex, are found in >90% of patients, but these autoantibodies are not thought to mediate the disease. In this article, we demonstrate highly frequent 21-hydroxylase-specific T cells detectable in 20 patients with Addison's disease. Using overlapping 18-aa peptides spanning the full length of 21-hydroxylase, we identified immunodominant CD8(+) and CD4(+) T cell responses in a large proportion of Addison's patients both ex vivo and after in vitro culture of PBLs ≤20 y after diagnosis. In a large proportion of patients, CD8(+) and CD4(+) 21-hydroxylase-specific T cells were very abundant and detectable in ex vivo assays. HLA class I tetramer-guided isolation of 21-hydroxylase-specific CD8(+) T cells showed their ability to lyse 21-hydroxylase-positive target cells, consistent with a potential mechanism for disease pathogenesis. These data indicate that strong CTL responses to 21-hydroxylase often occur in vivo, and that reactive CTLs have substantial proliferative and cytolytic potential. These results have implications for earlier diagnosis of adrenal failure and ultimately a potential target for therapeutic intervention and induction of immunity against adrenal cortex cancer. |
| spellingShingle | Dawoodji, A Chen, J Shepherd, D Dalin, F Tarlton, A Alimohammadi, M Penna-Martinez, M Meyer, G Mitchell, A Gan, E Bratland, E Bensing, S Husebye, E Pearce, S Badenhoop, K Kämpe, O Cerundolo, V High frequency of cytolytic 21-hydroxylase-specific CD8+ T cells in autoimmune Addison's disease patients. |
| title | High frequency of cytolytic 21-hydroxylase-specific CD8+ T cells in autoimmune Addison's disease patients. |
| title_full | High frequency of cytolytic 21-hydroxylase-specific CD8+ T cells in autoimmune Addison's disease patients. |
| title_fullStr | High frequency of cytolytic 21-hydroxylase-specific CD8+ T cells in autoimmune Addison's disease patients. |
| title_full_unstemmed | High frequency of cytolytic 21-hydroxylase-specific CD8+ T cells in autoimmune Addison's disease patients. |
| title_short | High frequency of cytolytic 21-hydroxylase-specific CD8+ T cells in autoimmune Addison's disease patients. |
| title_sort | high frequency of cytolytic 21 hydroxylase specific cd8 t cells in autoimmune addison s disease patients |
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