ABSTRACT
Objective To investigate the effect of Toxoplasma gondii excretory-secretory antigens (ESA) on CD4+ CD25+ Foxp3+ T (Treg) cells in mice carrying Lewis lung carcinoma, and examine the inhibitory effect of T. gondii ESA on tumor growth. Methods C57BL/6 mice were randomly assigned into the PBS group (n = 14) and the Lewis group (n = 34). Mice in the Lewis group were subcutaneously injected with 2 × 105 Lewis lung carcinoma cells in the right axilla, while animals in the PBS group were injected with the same volume of sterile PBS. On day 7 post-injection (D7), mice in the PBS group were further divided into the PBS2 group and the PBS2 + ESA group, of 7 mice in each group, and mice in the Lewis group were further divided into the Lewis2 group and the Lewis2 + ESA group, of 17 mice in each group. Then, mice in the PBS2 + ESA group and the Lewis2 + ESA group were intraperitoneally injected with 100 μL of ESA. The mouse spleen coefficient was calculated in each group 7 days post-injection with ESA, and the changes of Treg cell counts and the long-term tumor growth were measured in tumor-bearing mice. Results The spleen coefficient was significantly greater in the PBS2 + ESA group and the Lewis2 + ESA group than in the PBS2 (0.66% ± 0.09% vs. 0.30% ± 0.02%, P < 0.05) and Lewis2 groups (0.69% ± 0.07% vs. 0.33% ± 0.03%, P < 0.05) 7 days post-treatment with ESA, respectively, and the percentage of splenic Treg cells in splenocytes was significantly lower in the PBS2 + ESA group and the Lewis2 + ESA group than in the PBS2 (1.28% ± 0.14% vs. 2.06% ± 0.07%, P < 0.05) and Lewis2 groups (1.58% ± 0.14% vs. 2.44% ± 0.23%, P < 0.05), respectively. T. gondii ESA treatment caused a delay in tumor growth, and the tumor size was significantly smaller in the Lewis2 + ESA group than in the Lewis2 group (P < 0.05). Conclusion T. gondii ESA may reduce the proportion of splenic Treg cells in splenocytes and inhibit tumor growth in mice carrying Lewis lung carcinoma.
ABSTRACT
Objective To investigate the effect of Toxoplasma gondii excretory-secretory antigens (ESA) on CD4+ CD25+ Foxp3+ T (Treg) cells in mice carrying Lewis lung carcinoma, and examine the inhibitory effect of T. gondii ESA on tumor growth. Methods C57BL/6 mice were randomly assigned into the PBS group (n = 14) and the Lewis group (n = 34). Mice in the Lewis group were subcutaneously injected with 2 × 105 Lewis lung carcinoma cells in the right axilla, while animals in the PBS group were injected with the same volume of sterile PBS. On day 7 post-injection (D7), mice in the PBS group were further divided into the PBS2 group and the PBS2 + ESA group, of 7 mice in each group, and mice in the Lewis group were further divided into the Lewis2 group and the Lewis2 + ESA group, of 17 mice in each group. Then, mice in the PBS2 + ESA group and the Lewis2 + ESA group were intraperitoneally injected with 100 μL of ESA. The mouse spleen coefficient was calculated in each group 7 days post-injection with ESA, and the changes of Treg cell counts and the long-term tumor growth were measured in tumor-bearing mice. Results The spleen coefficient was significantly greater in the PBS2 + ESA group and the Lewis2 + ESA group than in the PBS2 (0.66% ± 0.09% vs. 0.30% ± 0.02%, P < 0.05) and Lewis2 groups (0.69% ± 0.07% vs. 0.33% ± 0.03%, P < 0.05) 7 days post-treatment with ESA, respectively, and the percentage of splenic Treg cells in splenocytes was significantly lower in the PBS2 + ESA group and the Lewis2 + ESA group than in the PBS2 (1.28% ± 0.14% vs. 2.06% ± 0.07%, P < 0.05) and Lewis2 groups (1.58% ± 0.14% vs. 2.44% ± 0.23%, P < 0.05), respectively. T. gondii ESA treatment caused a delay in tumor growth, and the tumor size was significantly smaller in the Lewis2 + ESA group than in the Lewis2 group (P < 0.05). Conclusion T. gondii ESA may reduce the proportion of splenic Treg cells in splenocytes and inhibit tumor growth in mice carrying Lewis lung carcinoma.
ABSTRACT
As most infections by the helminth parasite elicit the recruitment of CD4+CD25+Foxp3+ T (T(reg)) cells, many scientists have suggested that these cells could be used for the treatment of immune-mediated inflammation and associated diseases. In order to investigate the distribution and alteration of activated T(reg) cells, we compared the expression levels of T(reg) cell activation markers in the ileum and gastrocnemius tissues 1, 2, and 4 weeks after infection. The number of T(reg) cells was monitored using GFP-coded Foxp3 transgenic mice. In mice at 1 week after Trichinella spiralis infection, the number of activated T(reg) cells was higher than in the control group. In mice at 2 weeks after infection, there was a significant increase in the number of cells expressing Foxp3 and CTLA-4 when compared to the control group and mice at 1 week after infection. At 4 weeks after infection, T. spiralis was easily identifiable in nurse cells in mouse muscles. In the intestine, the expression of Gzmb and Klrg1 decreased over time and that of Capg remained unchanged for the first and second week, then decreased in the 4th week. However, in the muscles, the expression of most chemokine genes was increased due to T. spiralis infection, in particular the expression levels of Gzmb, OX40, and CTLA-4 increased until week 4. In addition, increased gene expression of all chemokine receptors in muscle, CXCR3, CCR4, CCR5, CCR9, and CCR10, was observed up until the 4th week. In conclusion, various chemokine receptors showed increased expressions combined with recruitment of T(reg) cells in the muscle tissue.
Subject(s)
Animals , Mice , Gene Expression , Helminths , Ileum , Inflammation , Intestines , Mice, Transgenic , Muscles , Parasites , Receptors, Chemokine , T-Lymphocytes, Regulatory , Trichinella spiralis , TrichinellaABSTRACT
BACKGROUND: Regulatory T cells (Treg) are able to inhibit the immunological response and maintain cutaneous immunological homeostasis, thus preventing autoimmunity against itself. In several studies, the importance of CD4+CD25+Foxp3+ Treg in psoriasis has been examined, using the peripheral blood of patients. However, limited studies on Treg are available and shows conflicting results. Recently, CD4+CD25-Foxp3+ T cells were identified as being the peripheral reservoir of CD4+CD25+Foxp3+ Treg. OBJECTIVE: The purpose of this study was to investigate differences in the CD4+CD25+Foxp3+ Treg and CD4+CD25- Foxp3+ T cell counts between patients with psoriasis and normal controls. METHODS: For phenotypic analysis, the proportions and absolute cell numbers of CD4+CD25+Foxp3+ Treg and CD4+CD25-Foxp3+ T cells in the peripheral blood were examined by flow cytometry. The correlation between the CD4+CD25+Foxp3+ Treg count and other parameters (age of onset, disease duration, BSA, psoriasis area and severity index score, and clinical stage) was also analyzed. RESULTS: Although the CD4+CD25+Foxp3+ Treg count was slightly increased while the number of CD4+CD25- Foxp3+ T cells was slightly decreased in psoriasis patients than that of the controls, the differences between the groups were not statistically significant (5.27+/-2.60 vs. 4.70+/-1.35, p>0.05; 1.56+/-1.07 vs. 1.93+/-1.08, p>0.05). The CD4+CD25+Foxp3+ Treg count did not correlate with the tested parameters except for the clinical stage of psoriasis. The mean+/-SD number of CD4+CD25+Foxp3+ Treg in the stable phase was higher than that in the progressive phase (7.26+/-2.58 vs. 4.35+/-2.10, p0.05). CONCLUSION: These findings suggest that the CD4+CD25+Foxp3+ Treg count alone is insufficient to explain the pathogenesis and severity of psoriasis. However, a decrease in circulating CD4+CD25+Foxp3+ Treg is likely to be correlated with an aggravation of psoriasis.
Subject(s)
Humans , Autoimmunity , Cell Count , Flow Cytometry , Homeostasis , Psoriasis , T-Lymphocytes , T-Lymphocytes, RegulatoryABSTRACT
BACKGROUND: Regulatory T cells (Treg) are able to inhibit the immunological response and maintain cutaneous immunological homeostasis, thus preventing autoimmunity against itself. In several studies, the importance of CD4+CD25+Foxp3+ Treg in psoriasis has been examined, using the peripheral blood of patients. However, limited studies on Treg are available and shows conflicting results. Recently, CD4+CD25-Foxp3+ T cells were identified as being the peripheral reservoir of CD4+CD25+Foxp3+ Treg. OBJECTIVE: The purpose of this study was to investigate differences in the CD4+CD25+Foxp3+ Treg and CD4+CD25- Foxp3+ T cell counts between patients with psoriasis and normal controls. METHODS: For phenotypic analysis, the proportions and absolute cell numbers of CD4+CD25+Foxp3+ Treg and CD4+CD25-Foxp3+ T cells in the peripheral blood were examined by flow cytometry. The correlation between the CD4+CD25+Foxp3+ Treg count and other parameters (age of onset, disease duration, BSA, psoriasis area and severity index score, and clinical stage) was also analyzed. RESULTS: Although the CD4+CD25+Foxp3+ Treg count was slightly increased while the number of CD4+CD25- Foxp3+ T cells was slightly decreased in psoriasis patients than that of the controls, the differences between the groups were not statistically significant (5.27+/-2.60 vs. 4.70+/-1.35, p>0.05; 1.56+/-1.07 vs. 1.93+/-1.08, p>0.05). The CD4+CD25+Foxp3+ Treg count did not correlate with the tested parameters except for the clinical stage of psoriasis. The mean+/-SD number of CD4+CD25+Foxp3+ Treg in the stable phase was higher than that in the progressive phase (7.26+/-2.58 vs. 4.35+/-2.10, p0.05). CONCLUSION: These findings suggest that the CD4+CD25+Foxp3+ Treg count alone is insufficient to explain the pathogenesis and severity of psoriasis. However, a decrease in circulating CD4+CD25+Foxp3+ Treg is likely to be correlated with an aggravation of psoriasis.