IL-2 is required for the activation of memory CD8+ T cells via antigen cross-presentation.
Dendritic cells (DCs) are capable of capturing exogenous Ag for the generation of MHC class I/peptide complexes. For efficient activation of memory CD8(+) T cells to occur via a cross-presentation pathway, DCs must receive helper signals from CD4(+) T cells. Using an in vitro system that reflects physiologic recall memory responses, we have evaluated signals that influence helper-dependent cross-priming, while focusing on the source and cellular target of such effector molecules. Concerning the interaction between CD4(+) T cells and DCs, we tested the hypothesis that CD40 engagement on DCs is critical for IL-12p70 (IL-12) production and subsequent stimulation of IFN-gamma release by CD8(+) T cells. Although CD40 engagement on DCs, or addition of exogenous IL-12 are both sufficient to overcome the lack of help, neither is essential. We next evaluated cytokines and chemokines produced during CD4(+) T cell/DC cross talk and observed high levels of IL-2 produced within the first 18-24 h of Ag-specific T cell engagement. Functional studies using blocking Abs to CD25 completely abrogated IFN-gamma production by the CD8(+) T cells. Although required, addition of exogenous IL-2 did not itself confer signals sufficient to overcome the lack of CD4(+) T cell help. Thus, these data support a combined role for Ag-specific, cognate interactions at the CD4(+) T cell/DC as well as the DC/CD8(+) T cell interface, with the helper effect mediated by soluble noncognate signals.
Blachère
Nathalie E
NE
The Rockefeller University, New York, NY 10021, USA.
Morris
Heather K
HK
Braun
Deborah
D
Saklani
Hélène
H
Di Santo
James P
JP
Darnell
Robert B
RB
Albert
Matthew L
ML
D016475:3T3 Cells; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism*; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D045142:Cross-Priming / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007156:Immunologic Memory / Q000235:genetics; D009980:Influenza A virus / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000502:physiology; D053707:Receptors, Interleukin-12; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000821:virology
D000956:Antigens, Viral; D019013:CD40 Antigens; D007376:Interleukin-2; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D007371:Interferon-gamma