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

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

Reinhold, Annegret¹  Bruder, Dunja¹  Podlasly, Lisa¹  Haberkorn, Oxana⁴  Annemann, Michaela⁵  Gereke, Marcus⁵  Kliche, Stefanie⁶  Schraven, Burkhart⁶ 

[1] and;..Department of Immune Control, Helmholtz Centre for Infection Research, Braunschweig, Germany;..Infection Immunology Group, Institute of Medical Microbiology, Infection Prevention and Control, Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany;Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany;Institute for Molecular and Clinical Immunology, Otto von Guericke University, Magdeburg, Germany

关键词: integrin;    adhesion;    infection;    Listeria monocytogenes;    influenza A virus;   

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

CC BY