Dendritic cells from old mice have a diminished capacity to activate CD8+ T cells.

ZACCA, E; CRESPO, MI; RUFAIL, M; MALETTO, B; PISTORESI-PALENCIA, MC; MORÓN, G

Santiago de Chile.

Congreso; Congreso Latinoamericano de Inmunologia; 2009

Sociedad Latinoamericana de Inmunología

DENDRITIC CELLS FROM OLD MICE HAVE A DIMINISHED CAPACITY TO ACTIVATE CD8+ T CELLS E Zacca 1 , M I Crespo 1 , M Rufail 1 , B Maletto 1 , M C Pistoresi 1 , G Morón 1 1CIBICI-CONICET, Fac. Ciencias Químicas, UNCórdoba<ezacca@fcq.unc.edu.ar> - CÓRDOBA Resumen : During aging, B and T cells manifest changes that affect their response to antigens (Ag). However, it is practically unkown how dendritic cells could participate in these changes. We have previously reported that DCs from 18/20-month-old mice (old, o) had a diminished ability to maturate in the presence of LPS as well as a lower capacity to cross present in vitro Ovalbumin (OVA) to an OVA-specific, MHC I restricted hybridoma (B3Z cells) compared to 2/3-month-old mice (young, y). We first studied the content of DCs in lymphoid organs. We found the following values (young vs old mice): popliteal lymph node (LN), 0.6±0.3 vs 0.7±0.5 (ns); mesenteric LN, 1.7±0.6 vs 3±1 (ns); spleen, 1.9±0.2 vs 1.2±0.2 (p<0.001); bone marrow, 2.1±0.4 vs 5.8±0.6 (p<0.0001); liver, 3±1 vs 6±4 (ns). Then we tested the ex vivo capacity of DC to cross-present OVA in old mice. We injected i.v. OVA coupled to latex beads and 2 hs later we purified the splenic DC from young and old mice and incubated them with B3Z cells. We found that oDCs had a very limited capacity to activate the hybridoma, compared to yDC. Then, we tested the capacity to activate naïve T cells, cultivating T cells from young OT-I mice with oDC or yDC incubated in vitro with OVA+PolyU/DOTAP. oDC stimulated a less stronger proliferative response (yDCs vs oDCs, 76.4±4.5 vs 16.0±15.1 % of OT-1 T cells in proliferation), CD25 expression (61.1±18.5 vs 17.0±10.3 % of OT-1 T cells) and IFNg secretion (11.6±5.4 vs 2.6±1.1 ng/mL) than yDC in OT-I T cells. Finally, we also found in the spleen of old mice 2 hs after injection i.v. with latex beads coupled to yellow green (YG), a lower proportion of YG+ DCs than in young mice. Altogether, these findings show that in spleen of old mice there is a lower content of DCs, which have a lower capacity to activate T cells than DCs from young mice. This deficiency could be related to a lower ability to capture Ag in vivo.