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Editor, Senior Moderator
Front Immunol. 2019 Oct 2;10:2351. doi: 10.3389/fimmu.2019.02351. eCollection 2019. [h=1].[/h]
Hornick EE[SUP]1[/SUP], Zacharias ZR[SUP]1[/SUP], Legge KL[SUP]1,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h] 1 Interdisciplinary Immunology Graduate Program, Department of Pathology, University of Iowa, Iowa City, IA, United States. 2 Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, United States.
[h=3]Abstract[/h] Influenza A virus (IAV) is a leading cause of respiratory infections, with increased risk of severe illness and death in the very young, aged, and immunocompromised individuals. In both mice and humans, IAV-specific T cell responses are protective during primary as well as homologous and heterologous challenge infections. Many mouse studies have focused on CD4 T cells specific for a single, known model or IAV antigen. However, studies have demonstrated that the IAV-specific CD4 T cell response comprises many epitopes spread across multiple viral proteins. Therefore, herein we track the antigen-experienced CD4 T cell response using the surrogate markers CD49d and CD11a. This novel surrogate marker method allows us to characterize the full IAV-specific CD4 T cell response without the potential bias that could occur when examining an individual Ag-specificity. Our findings demonstrate that the immunodominant I-A[SUP]b[/SUP]-binding NP[SUB]311-325[/SUB] epitope often used in studies of IAV-specific CD4 T cells represents only about 5% of the total IAV-specific CD4 T cell response. Further, we find that the kinetics of the full pulmonary CD4 T cell response is similar to that of NP[SUB]311[/SUB]-specific T cells and that the full CD4 T cell response in the lungs is predominantly composed of cells expressing the Th1 transcription factor T-bet, with smaller but significant portions of the response expressing the Treg and Tfh associated transcription factors Foxp3 and Bcl-6, respectively. Interestingly, although Th1 cells are the most abundant Th subset in the lungs of both BALB/c and C57Bl/6 mice following IAV, the relative abundance of Treg and Tfh is reversed in the different mouse strains. In BALB/c mice, Foxp3[SUP]+[/SUP] cells are more abundant than Bcl6[SUP]+[/SUP] cells, whereas in C57Bl/6 mice, there are more Bcl6[SUP]+[/SUP] cells. As a whole, these data highlight the diversity of the endogenous CD4 T cell response to a primary IAV infection, providing an important context for past and future studies of the IAV-specific CD4 T cell response.
Copyright ? 2019 Hornick, Zacharias and Legge.
[h=4]KEYWORDS:[/h] CD4 T cells; T helper subsets; adaptive immune response; influenza virus; pulmonary immunity
PMID: 31632414 PMCID: PMC6783515 DOI: 10.3389/fimmu.2019.02351
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Hornick EE[SUP]1[/SUP], Zacharias ZR[SUP]1[/SUP], Legge KL[SUP]1,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h] 1 Interdisciplinary Immunology Graduate Program, Department of Pathology, University of Iowa, Iowa City, IA, United States. 2 Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, United States.
[h=3]Abstract[/h] Influenza A virus (IAV) is a leading cause of respiratory infections, with increased risk of severe illness and death in the very young, aged, and immunocompromised individuals. In both mice and humans, IAV-specific T cell responses are protective during primary as well as homologous and heterologous challenge infections. Many mouse studies have focused on CD4 T cells specific for a single, known model or IAV antigen. However, studies have demonstrated that the IAV-specific CD4 T cell response comprises many epitopes spread across multiple viral proteins. Therefore, herein we track the antigen-experienced CD4 T cell response using the surrogate markers CD49d and CD11a. This novel surrogate marker method allows us to characterize the full IAV-specific CD4 T cell response without the potential bias that could occur when examining an individual Ag-specificity. Our findings demonstrate that the immunodominant I-A[SUP]b[/SUP]-binding NP[SUB]311-325[/SUB] epitope often used in studies of IAV-specific CD4 T cells represents only about 5% of the total IAV-specific CD4 T cell response. Further, we find that the kinetics of the full pulmonary CD4 T cell response is similar to that of NP[SUB]311[/SUB]-specific T cells and that the full CD4 T cell response in the lungs is predominantly composed of cells expressing the Th1 transcription factor T-bet, with smaller but significant portions of the response expressing the Treg and Tfh associated transcription factors Foxp3 and Bcl-6, respectively. Interestingly, although Th1 cells are the most abundant Th subset in the lungs of both BALB/c and C57Bl/6 mice following IAV, the relative abundance of Treg and Tfh is reversed in the different mouse strains. In BALB/c mice, Foxp3[SUP]+[/SUP] cells are more abundant than Bcl6[SUP]+[/SUP] cells, whereas in C57Bl/6 mice, there are more Bcl6[SUP]+[/SUP] cells. As a whole, these data highlight the diversity of the endogenous CD4 T cell response to a primary IAV infection, providing an important context for past and future studies of the IAV-specific CD4 T cell response.
Copyright ? 2019 Hornick, Zacharias and Legge.
[h=4]KEYWORDS:[/h] CD4 T cells; T helper subsets; adaptive immune response; influenza virus; pulmonary immunity
PMID: 31632414 PMCID: PMC6783515 DOI: 10.3389/fimmu.2019.02351
Free full text