Antigen Availability and DOCK2-Driven Motility Govern CD4+ T Cell Interactions with Dendritic Cells In Vivo.
J Immunol
; 199(2): 520-530, 2017 07 15.
Article
em En
| MEDLINE
| ID: mdl-28607113
ABSTRACT
Parenchymal migration of naive CD4+ T cells in lymph nodes (LNs) is mediated by the Rac activator DOCK2 and PI3Kγ and is widely assumed to facilitate efficient screening of dendritic cells (DCs) presenting peptide-MHCs (pMHCs). Yet how CD4+ T cell motility, DC density, and pMHC levels interdependently regulate such interactions has not been comprehensively examined. Using intravital imaging of reactive LNs in DC-immunized mice, we show that pMHC levels determined the occurrence and timing of stable CD4+ T cell-DC interactions. Despite the variability in interaction parameters, ensuing CD4+ T cell proliferation was comparable over a wide range of pMHC levels. Unexpectedly, decreased intrinsic motility of DOCK2-/- CD4+ T cells did not impair encounters with DCs in dense paracortical networks and, instead, increased interaction stability, whereas PI3Kγ deficiency had no effect on interaction parameters. In contrast, intravital and whole-organ imaging showed that DOCK2-driven T cell motility was required to detach from pMHClow DCs and to find rare pMHChigh DCs. In sum, our data uncover flexible signal integration by scanning CD4+ T cells, suggesting a search strategy evolved to detect low-frequency DCs presenting high cognate pMHC levels.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Linfócitos T CD4-Positivos
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Comunicação Celular
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Movimento Celular
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Proteínas Ativadoras de GTPase
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article