title: CD80 and CD86 differentially regulate mechanical interactions of T-cells with antigen-presenting dendritic cells and B-cells.
abstract: Functional T-cell responses are initiated by physical interactions between T-cells and antigen-presenting cells (APCs), including dendritic cells (DCs) and B-cells. T-cells are activated more effectively by DCs than by B-cells, but little is known about the key molecular mechanisms that underpin the particular potency of DC in triggering T-cell responses. To better understand the influence of physical intercellular interactions on APC efficacy in activating T-cells, we used single cell force spectroscopy to characterize and compare the mechanical forces of interactions between DC:T-cells and B:T-cells. Following antigen stimulation, intercellular interactions of DC:T-cell conjugates were stronger than B:T-cell interactions. DCs induced higher levels of T-cell calcium mobilization and production of IL-2 and IFNγ than were elicited by B-cells, thus suggesting that tight intercellular contacts are important in providing mechanically stable environment to initiate T-cell activation. Blocking antibodies targeting surface co-stimulatory molecules CD80 or CD86 weakened intercellular interactions and dampen T-cell activation, highlighting the amplificatory roles of CD80/86 in regulating APC:T-cell interactions and T-cell functional activation. The variable strength of mechanical forces between DC:T-cells and B:T-cell interactions were not solely dependent on differential APC expression of CD80/86, since DCs were superior to B-cells in promoting strong interactions with T-cells even when CD80 and CD86 were inhibited. These data provide mechanical insights into the effects of co-stimulatory molecules in regulating APC:T-cell interactions.
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (ASTAR), Singapore, Singapore. lim_tong_seng@immunol.a-star.edu.sg
authors.forename: Tong Seng
authors.initials: TS
authors.lastname: Lim
authors.forename: James Kang Hao
authors.initials: JK
authors.lastname: Goh
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mortellaro
authors.forename: Chwee Teck
authors.initials: CT
authors.lastname: Lim
authors.forename: Günter J
authors.initials: GJ
authors.lastname: Hämmerling
authors.forename: Paola
authors.initials: P
authors.lastname: Ricciardi-Castagnoli
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism*; D051940:B7-2 Antigen / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D019070:Cell Lineage; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D015395:Histocompatibility Antigens Class I; D002118:Calcium