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.
Cross-presentation of caspase-cleaved apoptotic self antigens in HIV infection / Pisana Moroni Rawson, ; Caroline, Molette; Melissa, Videtta; Laura, Altieri; Debora, Franceschini; Donato, Tiziana; Luigi, Finocchi; Antonella, Propato; Paroli, Marino; Francesca, Meloni; Mastroianni, Claudio Maria; D'Ettorre, Gabriella; John, Sidney; Alessandro, Sette; Barnaba, Vincenzo. - In: NATURE MEDICINE. - ISSN 1078-8956. - 13:12(2007), pp. 1431-1439. [10.1038/nm1679]
Cross-presentation of caspase-cleaved apoptotic self antigens in HIV infection
PAROLI, Marino;MASTROIANNI, Claudio Maria;Gabriella D'Ettorre;BARNABA, Vincenzo
2007
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.