Transient attenuated Foxp3 expression on CD4⁺ T cells treated with 7D4 mAb contributes to the control of parasite burden in DBA / 2 mice infected with lethal Plasmodium chabaudi chabaudi AS.

CD4(+) CD25(+) regulatory T (Treg) cells expressing Foxp3(+) play a critical role in maintaining immune homoeostasis and controlling excessive immune responses. However, controversy about the immunoregulatory role of Treg cells exists in malaria studies. Given the role of maintenance of Foxp3 expression in Treg cells' activities, we investigated whether anti-CD25 mAb (7D4 clone) treatment affects Foxp3 expression in CD4(+) T cells in DBA/2 mice infected with Plasmodium chabaudi chabaudi AS (P. c. chabaudi AS). We found that DBA/2 mice succumbed to P. c. chabaudi AS infection, which was accompanied by increased expression of Foxp3 in CD4(+) T cells at the peak parasitemia. In contrast, Foxp3 expression was impaired in CD25-depleted mice with 7D4 mAb treatment, leading to delayed parasitemia and extended survival of infected mice. Production of IFN-γ, TNF-α and IL-6, as well as NO was significantly enhanced in CD25-depleted mice. The majority of CD4(+) CTLA-4(+) cells expressed high levels of Foxp3 (Foxp3(hi) cells) in control mice with P. c. chabaudi AS infection. However, the number of CD4(+) Foxp3(hi) CTLA-4(+) cells was reduced in CD25-depleted mice. Together, these data suggest that CD4(+) Foxp3(hi) CTLA-4(+) cells may be involved in regulating the intensity of pro-inflammatory responses via CTLA-4.

Feng H ，Zhu XT ，Qi ZM ，Wang QH ，Wang GG ，Pan YY ，Li Y ，Zheng L ，Jiang YJ ，Shang H ，Cui L ，Cao YM ... -  《-》

Plasmodium chabaudi AS: distinct CD4(+)CD25(+)Foxp3(+) regulatory T cell responses during infection in DBA/2 and BALB/c mice.

Malaria infections display variation patterns of clinical course and outcome. Although CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells play an essential role in immune homeostasis, the immune regulatory roles involved in malaria infection remains to be elucidated. Herein, we compared the disparity in Treg cells response during the course of blood stage Plasmodium chabaudi chabaudi AS (P. c chabaudi AS) infection in DBA/2 and BALB/c mice. BALB/c mice initiated a Th1/Th2 profile respond to P. c chabaudi AS infection, but DBA/2 mice failed to control P. c chabaudi AS infection and almost of them died post-peak parasitemia. At the peak parasitemia, we found that higher proportion of Treg cells with elevated Foxp3 expression in DBA/2 than in BALB/c mice. We used anti-CD25 mAb to deplete Treg cells and found that the survival time and rate were prolonged in DBA/2 mice treated with anti-CD25 mAb. Treatment with anti-CD25 mAb in vivo led to enhanced pro-inflammation responses and Foxp3 expression decline on Treg cells. In contrast, after DBA/2 was treatment with anti-IL-10R mAb, IL-10R blockade in vivo caused excessive pro-inflammation responses and Foxp3 expression loss on CD4(+)CD25(+) T cells. Earlier death was found in all of DBA/2 mice with anti-IL-10R mAb. It suggested that IL-2 and IL-10 signal involved in maintaining Foxp3 expression on Treg cells. In all, the moderate suppressive activity of Treg cells may facilitate resistance to P. c chabaudi AS infection.

Wang GG ，Chen G ，Feng H ，Liu J ，Jiang YJ ，Shang H ，Cao YM ... -  《-》

IL-2 contributes to maintaining a balance between CD4+Foxp3+ regulatory T cells and effector CD4+ T cells required for immune control of blood-stage malaria infection.

Berretta F ，St-Pierre J ，Piccirillo CA ，Stevenson MM ... -  《-》

Natural regulatory (CD4+CD25+FOXP+) T cells control the production of pro-inflammatory cytokines during Plasmodium chabaudi adami infection and do not contribute to immune evasion.

Cambos M ，Bélanger B ，Jacques A ，Roulet A ，Scorza T ... -  《INTERNATIONAL JOURNAL FOR PARASITOLOGY》

Strong impact of CD4+ Foxp3+ regulatory T cells and limited effect of T cell-derived IL-10 on pathogen clearance during Plasmodium yoelii infection.

Abel S ，Lückheide N ，Westendorf AM ，Geffers R ，Roers A ，Müller W ，Sparwasser T ，Matuschewski K ，Buer J ，Hansen W ... -  《-》