Modulation of CD4 T cell function via CD6-targeting.
EBioMedicine
; 47: 427-435, 2019 Sep.
Article
en En
| MEDLINE
| ID: mdl-31481324
ABSTRACT
In recent years molecules involved on the immune synapse became successful targets for therapeutic immune modulation. CD6 has been extensively studied, yet, results regarding CD6 biology have been controversial, in spite of the ubiquitous presence of this molecule on virtually all CD4 T cells. We investigated the outcome of murine and human antibodies targeting CD6 domain 1. We found that CD6-targeting had a major impact on the functional specialization of CD4 cells, both human and murine. Differentiation of CD4 T cells towards a Foxp3+ Treg fate was prevented with increasing doses of anti-CD6, while Th1 polarization was favoured. No impact was observed on Th2 or Th17 specialization. These in vitro results provided an explanation for the dose-dependent outcome of in vivo anti-CD6 administration where the anti-inflammatory action is lost at the highest doses. Our data show that therapeutic targeting of the immune synapse may lead to paradoxical dose-dependent effects due to modification of T cell fate.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos T CD4-Positivos
/
Antígenos de Diferenciación de Linfocitos T
/
Antígenos CD
Límite:
Animals
/
Humans
Idioma:
En
Revista:
EBioMedicine
Año:
2019
Tipo del documento:
Article
País de afiliación:
Portugal