2. Academic Validation
  3. Modulation of CD4 T cell function via CD6-targeting

Modulation of CD4 T cell function via CD6-targeting

  • EBioMedicine. 2019 Sep;47:427-435. doi: 10.1016/j.ebiom.2019.08.008.
Raquel Filipa Freitas 1,  Afonso Basto 1,  Silvia C P Almeida 1,  Rita F Santos 2,  Carine M Gonçalves 3,  Jesus Corria-Osorio 4,  Tânia Carvalho 5,  Alexandre M Carmo 3,  Vanessa G Oliveira 1,  Kalet Leon 4,  Luis Graca 6
Affiliations

Affiliations

  • 1 Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; Instituto Gulbenkian de Ciência, Oeiras, Portugal.
  • 2 i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; IBMC - Instituto de Biologia Molecular e Celular, Porto, Portugal; Programa Doutoral em Biologia Molecular e Celular (MCbiology), Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Portugal.
  • 3 i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; IBMC - Instituto de Biologia Molecular e Celular, Porto, Portugal.
  • 4 Centro de Inmunologia Molecular, Havana, Cuba.
  • 5 Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
  • 6 Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; Instituto Gulbenkian de Ciência, Oeiras, Portugal. Electronic address: [email protected].
PMID: 31481324 DOI: 10.1016/j.ebiom.2019.08.008
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.

Keywords

CD4 T cells; CD6; EAE; Foxp3; T-cell polarization; Treg cells.

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