Competition within the virus-specific CD4 T-cell pool limits the T follicular helper response after influenza infection.
CD4 T follicular helper cells (TFH) are critical in the generation of potent and long-lived B-cell responses after viral infection. However, the factors that dictate the generation and maintenance of these cells are not fully understood. Here we use adoptive transfer of OTII T-cell receptor transgenic CD4 T cells, followed by infection with recombinant influenza A virus (IAV), as a means of identifying and tracking virus-specific CD4(+) T-cell responses. We show that T-cell competition within the virus-specific CD4 T-cell pool induced by IAV infection limits the proliferation and differentiation of IAV-specific CD4(+) TFH responses. In particular, increased T-cell competition for antigen results in a diminished IAV-specific TFH CD4 T-cell responses, particularly germinal center TFH responses. Strikingly, competition in the form of preexisting cellular immunity generated by heterosubtypic IAV immunization limits de novo CD4 T-cell responses in secondary lymphoid tissue. Taken together, these data show a profound linkage between antigen availability and promotion of TFH CD4(+) T-cell responses in response to infection. These data suggest that competition within the CD4 T-cell pool limits TFH responses and may be an important regulatory mechanism for controlling immunity.
Department of Microbiology and Immunology, The Peter Doherty Institute, The University of Melbourne, Parkville, Victoria, Australia.
Matthew R
MR
Olson
Department of Microbiology and Immunology, The Peter Doherty Institute, The University of Melbourne, Parkville, Victoria, Australia.
Brendon Y
BY
Chua
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
Kim L
0000-0003-1891-7274
KL
Good-Jacobson
Department of Microbiology and Immunology, The Peter Doherty Institute, The University of Melbourne, Parkville, Victoria, Australia.|St Jude Childrens Research Hospital, Memphis, TN, USA.
Peter C
PC
Doherty
Department of Microbiology and Immunology, The Peter Doherty Institute, The University of Melbourne, Parkville, Victoria, Australia.
David C
DC
Jackson
Department of Microbiology and Immunology, The Peter Doherty Institute, The University of Melbourne, Parkville, Victoria, Australia.|Department of Microbiology, Monash University, Clayton, Victoria, Australia.
Stephen J
SJ
Turner
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology; D002454:Cell Differentiation; D002455:Cell Division; D049109:Cell Proliferation; D002999:Clone Cells; D018858:Germinal Center / Q000166:cytology; D007109:Immunity; D009980:Influenza A virus / Q000276:immunology*; D008198:Lymph Nodes / Q000473:pathology; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D010641:Phenotype; D013045:Species Specificity; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000914:Antibodies, Viral; D000956:Antigens, Viral