| First Author | Balkow S | Year | 2010 |
| Journal | Blood | Volume | 116 |
| Issue | 11 | Pages | 1885-94 |
| PubMed ID | 20530790 | Mgi Jnum | J:164518 |
| Mgi Id | MGI:4834080 | Doi | 10.1182/blood-2009-05-224428 |
| Citation | Balkow S, et al. (2010) LFA-1 activity state on dendritic cells regulates contact duration with T cells and promotes T-cell priming. Blood 116(11):1885-94 |
| abstractText | A key event in the successful induction of adaptive immune responses is the antigen-specific activation of T cells by dendritic cells (DCs). Although LFA-1 (lymphocyte function-associated antigen 1) on T cells is considered to be important for antigen-specific T-cell activation, the role for LFA-1 on DCs remains elusive. Using 2 different approaches to activate LFA-1 on DCs, either by deletion of the alphaL-integrin cytoplasmic GFFKR sequence or by silencing cytohesin-1-interacting protein, we now provide evidence that DCs are able to make use of active LFA-1 and can thereby control the contact duration with naive T cells. Enhanced duration of DC/T-cell interaction correlates inversely with antigen-specific T-cell proliferation, generation of T-helper 1 cells, and immune responses leading to delayed-type hypersensitivity. We could revert normal interaction time and T-cell proliferation to wild-type levels by inhibition of active LFA-1 on DCs. Our data further suggest that cytohesin-1-interacting protein might be responsible for controlling LFA-1 deactivation on mature DCs. In summary, our findings indicate that LFA-1 on DCs needs to be in an inactive state to ensure optimal T-cell activation and suggest that regulation of LFA-1 activity allows DCs to actively control antigen-driven T-cell proliferation and effective immune responses. |
