The autoimmune immunopathology occurring in multiple sclerosis (MS) is sustained by myelin-specific and -nonspecific CD8+ T cells. We have previously shown that, in MS, activated T cells undergoing apoptosis induce a CD8+ T cell response directed against antigens that are unveiled during the apoptotic process, namely caspase-cleaved structural proteins such as non-muscle myosin and vimentin. Here, we have explored in vivo the development and the function of the immune responses to cryptic apoptosis-associated epitopes (AEs) in a well-established mouse model of MS, experimental autoimmune encephalomyelitis (EAE), through a combination of immunization approaches, multiparametric flow cytometry, and functional assays. First, we confirmed that this model recapitulated the main findings observed in MS patients, namely that apoptotic T cells and effector/memory AE-specific CD8+ T cells accumulate in the central nervous system of mice with EAE, positively correlating with disease severity. Interestingly, we found that AE-specific CD8+ T cells were present also in the lymphoid organs of unprimed mice, proliferated under peptide stimulation in vitro, but failed to respond to peptide immunization in vivo, suggesting a physiological control of this response. However, when mice were immunized with AEs along with EAE induction, AE-specific CD8+ T cells with an effector/memory phenotype accumulated in the central nervous system, and the disease severity was exacerbated. In conclusion, we demonstrate that AE-specific autoimmunity may contribute to immunopathology in neuroinflammation.

CD8+ T cells specific for cryptic apoptosis-associated epitopes exacerbate experimental autoimmune encephalomyelitis / Feizi, Neda; Focaccetti, Chiara; Pacella, Ilenia; Tucci, Gloria; Rossi, Alessandra; Costanza, Massimo; Pedotti, Rosetta; Sidney, John; Sette, Alessandro; La Rocca, Claudia; Procaccini, Claudio; Matarese, Giuseppe; Barnaba, Vincenzo; Piconese, Silvia. - In: CELL DEATH & DISEASE. - ISSN 2041-4889. - 12:11(2021). [10.1038/s41419-021-04310-6]

CD8+ T cells specific for cryptic apoptosis-associated epitopes exacerbate experimental autoimmune encephalomyelitis

Feizi, Neda;Focaccetti, Chiara;Pacella, Ilenia;Tucci, Gloria;Rossi, Alessandra;Sette, Alessandro;Matarese, Giuseppe;Barnaba, Vincenzo
;
Piconese, Silvia
2021

Abstract

The autoimmune immunopathology occurring in multiple sclerosis (MS) is sustained by myelin-specific and -nonspecific CD8+ T cells. We have previously shown that, in MS, activated T cells undergoing apoptosis induce a CD8+ T cell response directed against antigens that are unveiled during the apoptotic process, namely caspase-cleaved structural proteins such as non-muscle myosin and vimentin. Here, we have explored in vivo the development and the function of the immune responses to cryptic apoptosis-associated epitopes (AEs) in a well-established mouse model of MS, experimental autoimmune encephalomyelitis (EAE), through a combination of immunization approaches, multiparametric flow cytometry, and functional assays. First, we confirmed that this model recapitulated the main findings observed in MS patients, namely that apoptotic T cells and effector/memory AE-specific CD8+ T cells accumulate in the central nervous system of mice with EAE, positively correlating with disease severity. Interestingly, we found that AE-specific CD8+ T cells were present also in the lymphoid organs of unprimed mice, proliferated under peptide stimulation in vitro, but failed to respond to peptide immunization in vivo, suggesting a physiological control of this response. However, when mice were immunized with AEs along with EAE induction, AE-specific CD8+ T cells with an effector/memory phenotype accumulated in the central nervous system, and the disease severity was exacerbated. In conclusion, we demonstrate that AE-specific autoimmunity may contribute to immunopathology in neuroinflammation.
2021
autoimmunity; apoptosis; CD8 T cells
01 Pubblicazione su rivista::01a Articolo in rivista
CD8+ T cells specific for cryptic apoptosis-associated epitopes exacerbate experimental autoimmune encephalomyelitis / Feizi, Neda; Focaccetti, Chiara; Pacella, Ilenia; Tucci, Gloria; Rossi, Alessandra; Costanza, Massimo; Pedotti, Rosetta; Sidney, John; Sette, Alessandro; La Rocca, Claudia; Procaccini, Claudio; Matarese, Giuseppe; Barnaba, Vincenzo; Piconese, Silvia. - In: CELL DEATH & DISEASE. - ISSN 2041-4889. - 12:11(2021). [10.1038/s41419-021-04310-6]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1584005
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