Reduction of Foxp3+Cells by Depletion with the PC61 mAb Induces Mortality in Resistant BALB/c Mice Infected withToxoplasma gondii

Abstract

Regulatory T cells (Tregs) are CD4+Foxp3+ cells that modulate autoimmune responses. Tregs have been shown to be also involved during the immune response against infectious agents. The aim of this work is to study the role of Tregs during the infection with the intracellular protozoan Toxoplasma gondii. Resistant BALB/c mice were injected with 200 μg of anti-CD25 mAb (clone PC61) and 2 days later they were infected with 20 cysts of the ME49 strain of T. gondii. We observed that depleted mice showed 50–60% mortality during the acute infection. When FACS analysis was carried out, we observed that although injection of PC61 mAb eliminated 50% of Tregs, infected-depleted mice showed a similar percentage of CD25+Foxp3− (activated T cells, Tact) to those observed in infected nondepleted animals, demonstrating that in our depletion/infection system, injection of PC61 mAb did not hamper T cell activation while percentage of Tregs was reduced by 75% 10 days post infection. We concluded that Tregs are essential during protection in the acute phase of T. gondii infection.

Role of CD4+Foxp3+Regulatory T Cells in Protection Induced by a Live Attenuated, Replicating Type I Vaccine Strain of Toxoplasma gondii

“…Neither the number nor the frequency differed from that in the naive control group. A lack of Treg reduction seemed to contradict the uncontrolled immune response observed in the RH group and previous studies (14,18), showing that a decrease in Tregs was associated with mortality. However, we cannot exclude the possibility that this decrease appeared just before death or that it was significant only at the local site.…”

“…Type I strains are uniformly lethal except after attenuation, which leads to lower levels of replication and dissemination in the host and the development of long-term immunity, as for type II strains. Several studies have been performed to examine the role of Tregs using a susceptible C57BL/6 mouse strain (14,17,18,20) and a type II Toxoplasma strain. Decreased Foxp3 ϩ Treg counts at local and systemic sites were associated with such mortality in C57BL/6-susceptible mice after lethal oral infection with the type II strain (14).…”

“…This decrease occurred very shortly before the animals died and was correlated with virulence. When the dose and the route of infection were changed and the mice recovered (14,18), the decrease was only transient. In the present study, we investigated the Foxp3 ϩ Tregs after infection with the attenuated Mic1.3KO parasite and compared them with the Tregs from the parental RH type I strain, from which Mic1.3KO is derived.…”

“…They constitutively express the interleukin-2 (IL-2) receptor alpha chain (IL2R␣), a surface receptor also known as CD25, and the intracellular fork head box-p3 transcription factor (Foxp-3) marker (16). The role of Tregs after infection with type II strains has been fully described (14,(17)(18)(19)(20)(21), and Tregs have been clearly implicated in the mortality of C57BL/6 mice after oral infection in the lethal ileitis model (14). The collapse of Tregs is correlated with pathogenicity and occurs only under highly pathogenic conditions since oral infection of BALB/c mice with a type II strain did not induce a reduction in the levels of Tregs (14).…”

Partial depletion of CD4+CD25+Foxp3+ T regulatory cells significantly increases morbidity during acute phase Toxoplasma gondii infection in resistant BALB/c mice

“…It is noteworthy that despite the strikingly higher LP parasite burden in Treg cells depleted BALB/c mice, it was still considerably lower than the parasite burden seen in this tissue in B6 mice during acute infection. This may partially explain the acute phase survival of Treg cells depleted BALB/c mice in our study, although a previous study reported partial acute phase mortality after T. gondii ME49 strain infection of Treg cells depleted BALB/c mice [37]. Additional support for a protective role of Treg cells in T. gondii infection was obtained from the findings that BALB/c mice depleted for Treg cells had a strikingly higher brain parasite cyst burden, as opposed to non-treated mice.…”