In vitro initial immune response against Leishmania amazonensis infection is characterized by an increased production of IL-10 and IL-13

Multifunctional CD4+T cells in patients with American cutaneous leishmaniasis

“…We could not detect CD4 + that were able to produce IL‐10 and IFN‐γ simultaneously and did not observe any differences in the frequency of IL‐10 + CD4 + T cells, or in CD4 + CD25 high IL10 + regulatory T cells between LbAg and LaAg stimulation (data not shown). There are indications that L. amazonensis infection induces IL‐10 production by macrophages [51–53] and regulatory B cells [54], which were not evaluated in the present work. These possibilities are currently being investigated, as we are now also looking for IL‐10 production by other cell types.…”

“…Based on our data, we are very tempted to suggest that the quality of the Th1 response induced by L. amazonensis antigens, involving a poor generation of multifunctional CD4 + T cells and a high proportion of IFN‐γ single‐positive CD4 + T cells, in association with its well‐known capacity of inducing IL‐10 production [45–47,51,53,54], can be involved in the mechanisms responsible for the susceptibility to L. amazonensis observed in ATL patients and in experimental models. In this sense we have shown, for the first time, that multiparametric flow cytometry can bring new important aspects to the studies of ATL immunopathogenesis, and reinforce the importance of evaluating not just the magnitude, but the quality of a pathogen‐specific Th1 immune response by multiple parameters at a single‐cell level, to find better and more effective biomarkers of disease and protection.…”

“…Conversely, it has been demonstrated that LbAg is a more potent stimulator of T cell response than LaAg in individuals infected with L. amazonensis , as well as in individuals infected with parasites from the Viannia subgenus, before and after therapy [49]. It has also been shown that LaAg or live L. amazonensis promastigotes are able to induce high levels of IL‐10 in PBMCs obtained from LaAg‐vaccinated volunteers [50] or from healthy subjects [51], suggesting that the differences observed between LbAg and LaAg stimulation can be related to suppressive factors that are triggered by L. amazonensis parasites. We could not detect CD4 + that were able to produce IL‐10 and IFN‐γ simultaneously and did not observe any differences in the frequency of IL‐10 + CD4 + T cells, or in CD4 + CD25 high IL10 + regulatory T cells between LbAg and LaAg stimulation (data not shown).…”

“…LaAg stimulation induces a substantial amount of IFN‐γ single‐positive CD4 + T cells, which may not be sufficient to induce long‐term and good‐quality protection against reinfection, but could be effective when a rapid and transient Th1 response is needed, as in the case of immunotherapeutic interventions. It has also been shown that in‐vitro stimulation with LaAg in PBMCs obtained from LaAg vaccinated volunteers induce a higher number of IL‐10 producers (measured by ELISA) than IFN‐γ producers, while the opposite effect was observed in PBMCs from LTA patients before therapy [51]. The capacity of LaAg to induce IL‐10 secretion in PBMCs obtained from ATL patients, together with the generation of short‐lived IFN‐γ‐producing CD4 + T cells, could result in equilibrium between inflammatory and anti‐inflammatory responses, allowing parasite clearance and lesion resolution, as observed in the immunotherapeutic protocols tested so far.…”