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J Leukoc Biol. 2017 Feb;101(2):407-419. doi: 10.1189/jlb.1A0216-090RR. Epub 2016 Sep 7.

ADAP plays a pivotal role in CD4+ T cell activation but is only marginally involved in CD8+ T cell activation, differentiation, and immunity to pathogens.

Author information

1
Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.
2
Institute for Molecular and Clinical Immunology, Otto von Guericke University, Magdeburg, Germany.
3
Infection Immunology Group, Institute of Medical Microbiology, Infection Prevention and Control, Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany.
4
Institute for Molecular and Clinical Immunology, Otto von Guericke University, Magdeburg, Germany; burkhart.schraven@med.ovgu.de.
5
Department of Immune Control, Helmholtz Centre for Infection Research, Braunschweig, Germany; and.
6
Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany; dunja.bruder@med.ovgu.de.

Abstract

The adhesion and degranulation promoting adaptor protein (ADAP) is a multifunctional scaffold involved in many different signaling pathways that are important for the function of T cells, including the inside-out and outside-in signaling of integrins, the activation of NF-κB, and the subsequent production of proinflammatory cytokines (e.g., IFN-γ and IL-2). Strikingly, despite its well-established role in T cells, previous studies did not distinguish between CD4+ and CD8+ T cells, and thus, it is unknown whether ADAP fulfills equally important functions in both T cell subsets. We show here that despite comparable ADAP expression levels in CD4+ and CD8+ T cells, their function is differentially dependent on ADAP. Whereas in vitro TCR-stimulation experiments revealed that activation, proliferation, and adhesion are severely compromised in CD4+ T cells lacking ADAP, their CD8+ counterparts are hardly affected by ADAP deficiency. Accordingly, antigen-specific in vivo stimulation of adoptively transferred CD8+ T cells during Listeria monocytogenes (Lm) and influenza A virus (IAV) infection revealed only moderate effects of ADAP deficiency in terms of CD8+ T cell activation, proliferation, and differentiation, which, however, did not impair pathogen-specific immunity. Thus, we show for the first time that ADAP fulfills different functions in CD4+ and CD8+ T cells, with CD8+ T cells being less dependent on ADAP. Our data identify ADAP as a potential molecular target for T cell subset-specific therapeutic interventions.

KEYWORDS:

Listeria monocytogenes; adhesion; infection; influenza A virus; integrin

PMID:
27605210
DOI:
10.1189/jlb.1A0216-090RR
[Indexed for MEDLINE]

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