Role of GM-CSF in human DC differentiation

We investigated and obtained data on the interactions between human monocyte derived DCs (MDDC), generated in the presence of GM-CSF and IL-4 (IL-4 DC), and antigen-stimulated circulating gamma delta T lymphocytes, bearing the Vgamma2 TCR. Co-cultures of IFN-DCs with zoledronate-stimulated gamma delta T lymphocytes were also performed. gamma delta T-cell activation, as demonstrated by their up-modulation of activation marker expression levels (e.g. CD25 and CD69), was observed. These studies demonstrated for the first time the existence of a bidirectional activating interaction between DCs and gamma delta T lymphocytes activated by aminobiphosphonates. These data suggest a potential adjuvant role of this early cross-talk in the therapeutic activity of aminobiphosphonate drug that are currently used as anti-tumor drugs. A further characterization of the functional activities of activated gamma delta T lymphocytes and the reciprocal activation of the IFN-DCs are currently in progress.

In the context of a different research project, it was observed that GM-CSF can promote, in the absence of any other stimulus, the differentiation of human monocytes into dendritic cells. These GM-DCs are endowed with distinct immuno-stimulatory and migratory properties. In particular, GM-DCs are activated CD1a+ DCs expressing co-stimulatory molecules, MHC class I and II, able to induce the proliferation and IFN-gamma production of allogeneic T lymphocytes and to *migrate toward both inflammatory and homeostatic chemokines. Interestingly the responsiveness of individual donors to this DC-differentiation promoting activity of GM-CSF positively correlates with their basal expression level of GM-CSF receptor.

The results have been accepted for publication (Conti et al., EJI). The detailed protocol might be submitted to the knowledge portal.

• stimulus type
• Granulocyte macrophage colony-stimulating factor

• organism type
• Homo sapiens

• molecule type
• Major histocompatibility complex class II,
• CD69,
• aminobiphosphonates,
• Major histocompatibility complex class I,
• Interferon gamma,
• CD25 receptor,
• CD1a

• cell type
• gamma-delta t cell

• experimental design type
• cell type comparison experiment

created over 15 years ago (2 March 2009)    last modified over 13 years ago (28 September 2011)   [ RDF ]   [ RelFinder ]