Effective T-cell immune responses in the absence of the serine/threonine kinase RIP2.
The serine/threonine kinase RIP2 has been reported to be essential for Nod1 and Nod2 mediated cell activation, and has been suggested to play a role in the signaling cascade downstream of the T-cell receptor. We sought to ascertain the exact role of RIP2 in T-helper cell differentiation and CD8+ T-cell effector function in vivo and in vitro. In contrast to previous reports, we found that RIP2-deficient T cells did not exhibit impaired proliferation upon TCR engagement in vitro, and differentiation to cytokine producing Th1 or Th2 cells was normal in the absence of RIP2. These results were confirmed in vivo, as wild-type and RIP2-deficient virus-specific CD8+ T cells expanded comparably in mice after LCMV infection. Wild-type and RIP2-deficient CD4+ and CD8+ T cells from infected mice also showed similar proliferation and cytokine production when restimulated with full or partial agonist peptides ex vivo. Furthermore, no significant difference in adaptive T-cell responses could be observed between wild-type and RIP2-deficient mice after Listeria monocytogenes infection. Thus contrary to early reports, our data show that RIP2 is not an essential component of the TCR signaling machinery.
Nembrini
Chiara
C
Institute of Integrative Biology, Molecular Biomedicine, ETH Zürich, Swiss Federal Institute of Technology, Wagistrasse 27, CH-8952 Zurich-Schlieren, Switzerland.
Reissmann
Regina
R
Kopf
Manfred
M
Marsland
Benjamin J
BJ
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D018920:Coculture Techniques; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis; D008088:Listeriosis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000172:deficiency / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506255:Ripk2 protein, mouse