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.
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.
Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.|Institute for Molecular and Clinical Immunology, Otto von Guericke University, Magdeburg, Germany.
Gerald P
GP
Parzmair
Immune Regulation Group, 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.
Marcus
M
Gereke
Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Oxana
O
Haberkorn
Institute for Molecular and Clinical Immunology, Otto von Guericke University, Magdeburg, Germany.
Michaela
M
Annemann
Institute for Molecular and Clinical Immunology, Otto von Guericke University, Magdeburg, Germany.
Lisa
L
Podlasly
Institute for Molecular and Clinical Immunology, Otto von Guericke University, Magdeburg, Germany.
Stefanie
S
Kliche
Institute for Molecular and Clinical Immunology, Otto von Guericke University, Magdeburg, Germany.
Annegret
A
Reinhold
Institute for Molecular and Clinical Immunology, Otto von Guericke University, Magdeburg, Germany; burkhart.schraven@med.ovgu.de.|Department of Immune Control, Helmholtz Centre for Infection Research, Braunschweig, Germany; and.
Burkhart
B
Schraven
Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany; dunja.bruder@med.ovgu.de.|Infection Immunology Group, Institute of Medical Microbiology, Infection Prevention and Control, Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany.
Dunja
D
Bruder
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000276:immunology*; D002465:Cell Movement; D049109:Cell Proliferation; D000939:Epitopes / Q000276:immunology; D007109:Immunity; D007371:Interferon-gamma / Q000096:biosynthesis; D008089:Listeria monocytogenes / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019707:Receptors, Chemokine / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000939:Epitopes; C491468:Fyb protein, mouse; D019707:Receptors, Chemokine; D007371:Interferon-gamma
Listeria monocytogenes; adhesion; infection; influenza A virus; integrin