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


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.

SUBMITTER: Feizi N 

PROVIDER: S-EPMC8556378 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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CD8<sup>+</sup> T cells specific for cryptic apoptosis-associated epitopes exacerbate experimental autoimmune encephalomyelitis.

Feizi Neda N   Focaccetti Chiara C   Pacella Ilenia I   Tucci Gloria G   Rossi Alessandra A   Costanza Massimo M   Pedotti Rosetta R   Sidney John J   Sette Alessandro A   La Rocca Claudia C   Procaccini Claudio C   Matarese Giuseppe G   Barnaba Vincenzo V   Piconese Silvia S  

Cell death & disease 20211029 11


The autoimmune immunopathology occurring in multiple sclerosis (MS) is sustained by myelin-specific and -nonspecific CD8<sup>+</sup> T cells. We have previously shown that, in MS, activated T cells undergoing apoptosis induce a CD8<sup>+</sup> 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 respo  ...[more]

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