Skin-draining lymph node priming is sufficient to induce sterile immunity against pre-erythrocytic malaria.
Bottom Line: However, it has recently been demonstrated that priming also occurs in the skin.We wished to establish if sterile protection could be obtained in the absence of priming by infected hepatocytes.We then compared and contrasted the patterns of priming with those obtained by intradermal immunization, where priming occurs in the liver.
Affiliation: Inserm, UMR-S 945, Paris, France. firstname.lastname@example.orgShow MeSH
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Mentions: First, we assessed T-cell priming through the production of IFN-γ after stimulation by a specific parasite antigen, at different sites in i.d.-immunized mice, where priming is expected to occur concomitantly in the skin, the liver and the spleen, and in s.c.-immunized mice, where priming is expected to occur principally, or entirely, in the skin. Groups of BALB/c, Cd81−/− or Cd81+/+ mice were immunized s.c. or i.d. with γ-spz. Cells were harvested from different sites for the IFN-γ assays. iLN cells from either s.c.- or i.d.-immunized mice showed strong IFN-γ production, following stimulation with a CS epitope, which contrasted with the weak IFN-γ production by iLN cells isolated from PyWT infected mice (Fig 2A). However, activated T cells could leave the priming site and circulate to other lymph nodes and organs within few days (4–5 days) after i.d. vaccination (Chakravarty et al, 2007). Consequently, we additionally sought the presence of activated T cells in the contra-lateral non-draining inguinal-lymph node (nLN), the celiac-lymph node (cLN) and the spleen. Five days after s.c. or i.d. vaccination with γ-spz, IFN-γ-producing T cells were equally present in the iLN, nLN, cLN and the spleen (Fig 2B). This could either be due to migration of activated T cells from the priming site in the skin (iLN) to the nLN, cLN and the spleen, or due to the presence of multiple priming sites. In order to distinguish between the two possibilities, migration of T lymphocytes out of the priming site was inhibited. This was achieved by treating mice with the immunosuppressive drug FTY720, which downregulates the expression of sphingosine-1-phosphate receptors (S1PRs) on the T lymphocyte surface, thereby preventing lymphocytes from migrating along a S1P gradient and reducing the T-cell egress from draining-lymph nodes (Brinkmann et al, 2010). In the i.d.- or s.c.-vaccinated and FTY720-treated mice, the level of activated T cells in the iLN increased about twofolds in contrast to the nLN, where activated T cells were no longer found (Fig 2B). Furthermore, treatment with FTY720 also reduced the level of activated T cells in the cLN and the spleen to negligible levels in the s.c.-immunized mice but not in the i.d.-immunized mice, where their levels increased about 1.5-fold (Fig 2B). These data suggest that whereas the iLN, CLN and the spleen are all priming sites in i.d.-immunized mice, in s.c.-immunized mice priming occurs mainly, if not exclusively, in the skin-draining lymph nodes (iLN).
Affiliation: Inserm, UMR-S 945, Paris, France. email@example.com