MYELOID IMMATURE CELLS (GR-1+CD11B+) ACQUIRE THEIR INHIBITORY PROPERTIES IN THE BONE MARROW, AND MIGRATE TO LYMPH NODES TO EXERT THEIR FUNCTION

LANDONI V; MARTIRE GRECO D; RODRIGUEZ-RODRIGUES N; CHIARELLA P; SCHIERLOH P; REARTE B; ISTURIZ MA; FERNÁNDEZ G

Mar del Plata

Congreso; LXII Reunión Anual de la Sociedad Argentina de Inmunología; 2014

Sociedad Argentina de Inmunología (SAI)

Lymph nodes (LN) from LPS-immunosuppressed (IS) mice have a decreased T cell (Ly) proliferation, associated to an increment of myeloid derived suppressor cells (MDSC, Gr-1+CD11b+). Moreover, MDSC from bone marrow (BM) of IS mice also exhibited an inhibitory activity towards Ly proliferation. Our aim was to evaluate whether MDSC acquire their immunosuppressive properties in BM and then migrate to LN to exert their function, and evaluate their inhibitory mechanisms. We found that the inhibition of Ly proliferation by BM-IS was accompanied with an increase in cells expressing inducible nitric oxide (NO) synthase (Gr-1+CD11b+iNOS+) and reactive oxygen species (ROS) (Gr-1+CD11b+DHR+) determined by FACS (p 0.05). When iNOS and ROS were blocked (using L-NAME or Catalase), Ly proliferation was restored to control levels. To determine whether BM Gr- 1+CD11b+ cells from IS mice migrate to LN in vivo, Ctrl and IS BM cells were stained with CFSE and injected i.v. to Ctrl and IS mice in all possible combinations. After 3h, LN were collected and the % of Gr-1+CD11b+CFSE+ cells was measured by FACS. We found an increased percentage of Gr-1+CD11b+CFSE+ cells in LN only when BM-IS cells were injected to IS mice (p 0.05). Accordingly, BM-IS cells showed an increased CCR7 expression, a chemokine receptor involved in migration to LN (p 0.05). Alternatively, the chemoattractant activity of LN was assayed using conditioned media (CM) from Ctrl or IS LN in a transwell system. The % and number of migrated Gr-1+CD11b+ cells was higher in the presence of IS LN CM (p 0.05). Finally, we found that soluble factors present in the CM from BM of IS mice were able to transform Ctrl BM cells into inhibitory cells towards Ly proliferation (p 0.05). These results indicate that soluble factors from IS-BM are necessary to induce inhibitory properties in Gr-1+CD11b+ cells and that the ability of these cells to migrate to LN resides both in the cell itself and in signals delivered from the IS context.