title: Primary induction of CD4 T cell responses in nasal associated lymphoid tissue during group A streptococcal infection.
abstract: CD4 T cells are important for development of long-term immunity to bacterial infections. Here we describe construction of a group A streptococcus (GAS) strain that expresses the model ovalbumin epitope (OVA) on its surface, and the use of this strain in adoptive transfer experiments to study CD4 T cell response to bacterial infection in nasal-associated lymphoid tissue (NALT), which was previously shown to be a specific target for GAS colonization. The OVA(+) GAS, but not the wild-type strain was shown to activate CD4 T cells in an antigen-specific manner both in vitro and in vivo. After intranasal infection of mice with this strain, OVA-specific CD4 T cells were first activated in NALT, which is functionally equivalent to human tonsils, rather than in the cervical lymph nodes. During localized infection, OVA(+) GAS induced rapid and prolonged activation of CD4 T cells at higher magnitudes in the NALT than in draining lymph nodes and spleen, where CD4 T cells underwent little or no activation. In contrast, systemic infection induced significantly higher activation of CD4 T cells in both lymph nodes and spleens, compared to when the infection was localized in NALT. Further investigation of cellular immune responses in NALT during GAS infection using adoptive T cell transfer, combined with the model antigen on the pathogen may ultimately shed light on mechanisms for failure of children to develop protective immune responses following streptococcal tonsillitis.
authors.affiliation: Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. hspark@lenti.med.umn.edu
authors.forename: Hae-Sun
authors.initials: HS
authors.lastname: Park
authors.forename: Massimo
authors.initials: M
authors.lastname: Costalonga
authors.forename: R Lee
authors.initials: RL
authors.lastname: Reinhardt
authors.forename: Priscilla E
authors.initials: PE
authors.lastname: Dombek
authors.forename: Marc K
authors.initials: MK
authors.lastname: Jenkins
authors.forename: P Patrick
authors.initials: PP
authors.lastname: Cleary
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology*; D051379:Mice; D009666:Nose / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D013290:Streptococcal Infections / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D011993:Recombinant Fusion Proteins; C014689:streptococcal M protein; D010047:Ovalbumin