Title | Cross-presentation of caspase-cleaved apoptotic self antigens in HIV infection. |
Publication Type | Journal Article |
Year of Publication | 2007 |
Authors | Rawson, PMoroni, Molette, C, Videtta, M, Altieri, L, Franceschini, D, Donato, T, Finocchi, L, Propato, A, Paroli, M, Meloni, F, Mastroianni, CM, d'Ettorre, G, Sidney, J, Sette, A, Barnaba, V |
Journal | Nat Med |
Volume | 13 |
Issue | 12 |
Pagination | 1431-9 |
Date Published | 2007 Dec |
ISSN | 1546-170X |
Keywords | Adult, Antigen Presentation, Apoptosis, Caspases, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cytoskeleton, Dendritic Cells, Epitopes, Female, HIV Infections, Humans, Male, Middle Aged, Vimentin |
Abstract | We found that the proteome of apoptotic T cells includes prominent fragments of cellular proteins generated by caspases and that a high proportion of distinct T cell epitopes in these fragments is recognized by CD8+ T cells during HIV infection. The frequencies of effector CD8+ T cells that are specific for apoptosis-dependent epitopes correlate with the frequency of circulating apoptotic CD4+ T cells in HIV-1-infected individuals. We propose that these self-reactive effector CD8+ T cells may contribute to the systemic immune activation during chronic HIV infection. The caspase-dependent cleavage of proteins associated with apoptotic cells has a key role in the induction of self-reactive CD8+ T cell responses, as the caspase-cleaved fragments are efficiently targeted to the processing machinery and are cross-presented by dendritic cells. These findings demonstrate a previously undescribed role for caspases in immunopathology. |
DOI | 10.1038/nm1679 |
Alternate Journal | Nat. Med. |
PubMed ID | 18026114 |
Cross-presentation of caspase-cleaved apoptotic self antigens in HIV infection.
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