PMID- 16751372 OWN - NLM STAT- MEDLINE DCOM- 20060713 LR - 20190516 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 176 IP - 12 DP - 2006 Jun 15 TI - IL-2 is required for the activation of memory CD8+ T cells via antigen cross-presentation. PG - 7288-300 AB - 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. FAU - Blachere, Nathalie E AU - Blachere NE AD - The Rockefeller University, New York, NY 10021, USA. FAU - Morris, Heather K AU - Morris HK FAU - Braun, Deborah AU - Braun D FAU - Saklani, Helene AU - Saklani H FAU - Di Santo, James P AU - Di Santo JP FAU - Darnell, Robert B AU - Darnell RB FAU - Albert, Matthew L AU - Albert ML LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Antigens, Viral) RN - 0 (CD40 Antigens) RN - 0 (Interleukin-2) RN - 0 (Receptors, Interleukin) RN - 0 (Receptors, Interleukin-12) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - 3T3 Cells MH - Animals MH - Antigens, Viral/immunology/*metabolism MH - CD40 Antigens/immunology/metabolism/physiology MH - CD8-Positive T-Lymphocytes/*immunology/*metabolism/virology MH - Cell Differentiation/genetics/immunology MH - Cells, Cultured MH - *Cross-Priming/genetics MH - Dendritic Cells/cytology/immunology/metabolism MH - *Immunologic Memory/genetics MH - Influenza A virus/*immunology MH - Interferon-gamma/biosynthesis MH - Interleukin-2/deficiency/genetics/*physiology MH - *Lymphocyte Activation/genetics MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Receptors, Interleukin/physiology MH - Receptors, Interleukin-12 MH - Signal Transduction/genetics/immunology MH - T-Lymphocytes, Helper-Inducer/immunology/virology EDAT- 2006/06/06 09:00 MHDA- 2006/07/14 09:00 CRDT- 2006/06/06 09:00 PHST- 2006/06/06 09:00 [pubmed] PHST- 2006/07/14 09:00 [medline] PHST- 2006/06/06 09:00 [entrez] AID - 176/12/7288 [pii] AID - 10.4049/jimmunol.176.12.7288 [doi] PST - ppublish SO - J Immunol. 2006 Jun 15;176(12):7288-300. doi: 10.4049/jimmunol.176.12.7288.