Increases in Superantigen-specific Treg cells during MMTV infection are TLR4 dependent

G CABRERA; D BURZYN; M C COURREGES; J MUNDIÑANO; G CAMICIA; D LORENZO; AF MAGLIOCO; S ROSS; I NEPOMNASCHY; I PIAZZON

Río de Janeiro, Brasil

Congreso; InmunoRío 2007; 2007

Latin American Association for Immunology

Mouse Mammary Tumor Virus (MMTV) is transmitted during lactation and its infection depends on the presentation of a superantigen (Sag) by dendritic and B cells to Sag-reactive T cells. BALB/c mice were foster-nursed on mothers infected with MMTV(LA) which encodes for Sag derived from the hypervariable region of Mtv-7. Here, we demonstrated by FACS that during the first week of infection the virus produces an increase in the percentage and absolute number of Vb6+Foxp3+CD25+ Regulatory T Cells (Treg) reactive to Sag in Peyer´s Patches (PPs). Increases were detected both in Foxp3+CD25+ and in Foxp3+CD25- subset -a Treg reservoir-. In addition, back-crossing experiments showed that in absence of Vb6+ T cells, the percentage of Foxp3+ T cells was decreased. Using CD11c-DTR transgenic and C3H/HeJ mice we showed that the increase in Treg cells was dependent on the presence of dendritic cells and a functional Toll Like Receptor 4 molecule (TLR4). Since on day 6 of infection more than 80% of CD4+CD25+ cells are Foxp3+, CD4+CD25+ cells were purified by MACS in order to study their suppressor capacity in mixed lymphocyte reactions using stimulator cells from AKR/J (Mtv-7+) or C3H/HeN (Mtv-7-). Proliferation was inhibited by CD4+CD25+ cells only when the responder cells were stimulated with the viral Sag. These results show that MMTV induces in PPs an early increase in the number of Treg cells reactive to Sag in a TLR4 dependent manner. The role of Treg as assessed by depletion of CD25+ cells before and during in vivo infection is discussed.