Autistic effector T cells in mice with a point mutation in the LAT adaptor fail to respond to Listeria monocytogenes infection

• Published in: International immunology 2005-07, Vol.17 (7), p.951-957
• Main Authors: Prinz, Immo, Kursar, Mischo, Mittrücker, Hans-Willi, Aguado, Enrique, Steinhoff, Ulrich, Kaufmann, Stefan H. E., Malissen, Bernard
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - immunology; Animals; APC allophycocyanin; CFSE carboxyfluorescein diacetate; Immunology; LatY136F mutation; LAT linker for activation of T cells; Life Sciences; linker for activation of T cells (LAT); Listeria monocytogenes; Listeria monocytogenes - immunology; Listeriosis - genetics; Listeriosis - immunology; LLO Listeriolysin O; LmOVA Listeria monocytogenes-expressing ovalbumin; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Membrane Proteins - genetics; Membrane Proteins - immunology; Mice; Mice, Mutant Strains; Phosphoproteins - genetics; Phosphoproteins - immunology; PLC-γ1 phospholipase C-γ1; PMA phorbol myristate acetate; Point Mutation - genetics; Point Mutation - immunology; signal transduction; succinimidyl ester; T cell activation; T-Lymphocytes - immunology; Th1/Th2 cells; TSB tryptic soy broth
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxh276

The adaptor protein linker for activation of T cells (LAT) is an important transducer of extracellular T cell stimuli. In mice with a point mutation in LAT (LatY136F), TCR signaling is substantially compromised and LatY136F T cells are unresponsive to CD3 cross-linking in vitro. Nevertheless, LatY136F mice develop a polyclonal lymphoproliferation of CD4+ T cells, which display a Th2-polarized effector phenotype. In this study, LatY136F mice were infected with the intracellular bacterium Listeria monocytogenes and the antigen-specific responses of T cells were determined. Both CD4+ and CD8+ LatY136F T cells were unresponsive to L. monocytogenes infection. In contrast, when CD4+ T cells from wild-type mice were adoptively transferred into LatY136F hosts, they responded normally to L. monocytogenes, indicating that the LatY136F milieu permits Th1 responses. Furthermore, we analyzed whether the infection would influence the capacity of LatY136F CD4+ T cells to produce IL-4 and IFN-γ. While L. monocytogenes infection results in Th1-type T cell responses in wild-type animals, we found that it did not shift the strong Th2 polarization of LatY136F T cells towards a Th1 pattern. In conclusion, our results suggest that the activation and Th2 polarization of the LatY136F CD4+ T cells is not influenced by infection with an intracellular pathogen known to induce robust Th1 responses, and is thus likely driven by T cell intrinsic mechanisms.