CD154+ CD4+ T-cell dependence for effective memory influenza virus-specific CD8+ T-cell responses.
CD40-CD154 (CD40 ligand) interactions are essential for the efficient priming of CD8(+) cytotoxic T lymphocyte (CTL) responses. This is typically via CD4(+)CD154(+) T-cell-dependent 'licensing' of CD40(+) dendritic cells (DCs); however, DCs infected with influenza A virus (IAV) upregulate CD154 expression, thus enabling efficient CTL priming in the absence of CD4(+) T activation. Therefore, it is unclear whether CD4 T cells and DCs have redundant or unique roles in the priming of primary and secondary CTL responses after infection. Here we determine the precise cellular interactions involved in CD40-CD154 regulation of both primary and secondary IAV-specific CTL responses. Infection of both CD40 KO and CD154 KO mice resulted in diminished quantitative and qualitative CTL responses after both primary and secondary infection. Adoptive transfer of CD154(+), but not CD154 KO, CD4 T cells into CD154 KO mice restored both primary and secondary IAV-specific CD8 T-cell responses. These data show that, although CD154 expression on CD4 T cells and other cell types (that is, DCs) may be redundant for the priming of primary CTL responses, CD154 expression by CD4 T cells is required for the priming memory CD8 T cells that are capable of fully responding to secondary infection.
Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
Matthew R
MR
Olson
Division of Immunology, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Shirley Gk
SG
Seah
Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
Kathryn
K
Edenborough
1] Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia [2] Department of Immunology, St Judes Childrens Research Hospital, Memphis, TN, USA.
Peter C
PC
Doherty
Division of Immunology, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Andrew M
AM
Lew
Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
Stephen J
SJ
Turner
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D019013:CD40 Antigens / Q000172:deficiency / Q000235:genetics; D023201:CD40 Ligand / Q000172:deficiency / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002450:Cell Communication / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000821:virology; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D019013:CD40 Antigens; D023201:CD40 Ligand