TY - JOUR
T1 - Primary induction of CD4 T cell responses in nasal associated lymphoid tissue during group A streptococcal infection
AU - Park, Hae Sun
AU - Costalonga, Massimo
AU - Reindhart, R. Lee
AU - Dombek, Priscilla E.
AU - Jenkins, Marc
AU - Cleary, P. Patrick
PY - 2004/10
Y1 - 2004/10
N2 - 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 W 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.
AB - 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 W 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.
KW - CD4 T cells
KW - GAS
KW - NALT
KW - Rodents
UR - http://www.scopus.com/inward/record.url?scp=7244231206&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=7244231206&partnerID=8YFLogxK
U2 - 10.1002/eji.200425242
DO - 10.1002/eji.200425242
M3 - Article
C2 - 15368301
AN - SCOPUS:7244231206
SN - 0014-2980
VL - 34
SP - 2843
EP - 2853
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 10
ER -