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.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Parzmair GP,Gereke M,Haberkorn O,Annemann M,Podlasly L,Kliche S,Reinhold A,Schraven B,Bruder Ddoi
10.1189/jlb.1A0216-090RRsubject
Has Abstractpub_date
2017-02-01 00:00:00pages
407-419issue
2eissn
0741-5400issn
1938-3673pii
jlb.1A0216-090RRjournal_volume
101pub_type
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