CD80 and CD86 differentially regulate mechanical interactions of T-cells with antigen-presenting dendritic cells and B-cells

• Published in: PloS one 2012-09, Vol.7 (9), p.e45185-e45185
• Main Authors: Lim, Tong Seng, Goh, James Kang Hao, Mortellaro, Alessandra, Lim, Chwee Teck, Hämmerling, Günter J, Ricciardi-Castagnoli, Paola
• Format: Article
• Language: English
• Subjects: Activation; Animals; Antibodies; Antigen Presentation - immunology; Antigen-presenting cells; Antigens; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B7-1 Antigen - metabolism; B7-2 Antigen - metabolism; Biology; Blocking antibodies; Calcium; Calcium - metabolism; Calcium mobilization; CD80 antigen; CD86 antigen; Cell activation; Cell Communication - immunology; Cell interactions; Cell Lineage; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Histocompatibility Antigens Class I - metabolism; Immunoglobulins; Immunology; Immunophenotyping; Interleukin 2; Kinases; Laboratory animals; Lipids; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes B; Lymphocytes T; Mechanical stimuli; Medical research; Medicine; Mice; Mice, Knockout; Microscopy; Molecular modelling; Peptides; Physiological aspects; Silicon nitride; Spectroscopy; T cell receptors; T cells; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0045185

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.