Tolerization of recent thymic emigrants is required to prevent RBC-specific autoimmunity.
J Autoimmun
; 114: 102489, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-32507505
ABSTRACT
Autoimmune hemolytic anemia (AIHA) leads to accelerated destruction of autologous red blood cells (RBCs) by autoantibodies. AIHA is a severe and sometimes fatal disease. While there are several therapeutic strategies available, there are currently no licensed treatments for AIHA and few therapeutics result in treatment-free durable remission. The etiology of primary AIHA is unknown; however, secondary AIHA occurs concurrently with lymphoproliferative disorders and infections. Additionally, AIHA is the second most common manifestation of primary immunodeficiency disorders and has been described as a side effect of checkpoint inhibitor therapy. Given the severity of AIHA and the lack of treatment options, understanding the initiation of autoimmunity is imperative. Herein, we utilized a well-described model of RBC biology to dissect how RBC-specific autoreactive T cells become educated against RBC autoantigens. We show that, unlike most autoantigens, T cells do not encounter RBC autoantigens in the thymus. Instead, when they leave the thymus as recent thymic emigrants (RTEs), they retain the ability to positively respond to RBC autoantigens; only after several weeks in circulation do RTEs become nonresponsive. Together, these data suggest that any disruption in this process would lead to breakdown of tolerance and initiation of autoimmunity. Thus, RTEs and this developmental process are potential targets to prevent and treat AIHA.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Timo
/
Linfócitos T
/
Autoimunidade
/
Movimento Celular
/
Eritrócitos
/
Tolerância Imunológica
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Autoimmun
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos