European Congress of Immunology Glasgow, 5 - 8 September, 2012.
Abstract
Purpose/Objective: The non-classical HLA class I molecule HLA-G
was initially shown to play a major role in feto-maternal tolerance.
Since this discovery, it has been established that HLA-G is a tolerogenic
molecule, which participates to the control of the immune response.
HLA-G inhibits a wide array of immune cells and has long-term immune-
modulatory effects since it can induce the generation of suppressor/
regulatory cells. We recently demonstrated that tolerogenic
DC, termed DC-10, promote the differentiation of Tr1 cells via the
IL10-dependent membrane bound HLA-G1/ILT4 pathway. The role of
membrane-bound HLA-G1 in promoting Tr1 cells via DC-10, raise the
question whether soluble shed HLA-G1 or HLA-G5 can promote Tr1
cell differentiation.
Materials and methods: Human naı¨ve CD4+ T cells were stimulated
via anti-CD3 mAbs cross-linked on artificial APC consisting in murine
L-cells co-transfected with human CD32, CD80, and CD58 in the
presence of shed sHLA-G1 or HLA-G5 alone or in combination with
IL-10. As control, we used Th0 and Tr1 cells differentiated with
artificial APC alone or in the presence of IL-10 and IFN-a, respectively.
Results: We showed that repetitive stimulation of human naı¨ve CD4+
T cells in the presence of shed HLA-G1 or HLA-G5, alone or in
combination with IL-10, induced the differentiation of a population of
CD4+ T cells that are phenotypically different from both Th0 and Tr1
cells. T cells differentiated with soluble HLA-Gs secrete lower levels of
IFN-g and IL-2 as compared to Th0 cells. Interestingly, HLA-Ginduced
T cells secrete low amounts of IL-10, which is slightly
increased when IL-10 is present in culture, but never reach the levels
produced by Tr1 cells. Despite the ability to proliferate upon
polyclonal activation, HLA-G-induced T cells suppress the proliferation
of autologous CD4+ T cells in vitro.
Conclusions: We showed that activation of human CD4+ T cells in
the presence of both soluble shed HLA-G1 or HLA-G5, alone or in
combination with IL-10, promotes the induction of a population of
suppressor CD4+ T cells, which are distinct from Tr1 cells
