Autistic effector T cells in mice with a point mutation in the LAT adaptor fail to respond to Listeria monocytogenes infection.
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 T(h)2-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 T(h)1 responses. Furthermore, we analyzed whether the infection would influence the capacity of LatY136F CD4(+) T cells to produce IL-4 and IFN-gamma. While L. monocytogenes infection results in T(h)1-type T cell responses in wild-type animals, we found that it did not shift the strong T(h)2 polarization of LatY136F T cells towards a T(h)1 pattern. In conclusion, our results suggest that the activation and T(h)2 polarization of the LatY136F CD4(+) T cells is not influenced by infection with an intracellular pathogen known to induce robust T(h)1 responses, and is thus likely driven by T cell intrinsic mechanisms.
Prinz
Immo
I
Centre d'Immunologie de Marseille-Luminy, INSERM-CNRS-Université de la Méditerranée, Parc Scientifique de Luminy, Case 906, 13288 Marseille Cédex 9, France.
Kursar
Mischo
M
Mittrücker
Hans-Willi
HW
Aguado
Enrique
E
Steinhoff
Ulrich
U
Kaufmann
Stefan H E
SH
Malissen
Bernard
B
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology*; D000818:Animals; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology*; D017354:Point Mutation / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins