Unteer. doi:10.1371/journal.pone.0051819.gIL-17 secreted by Th17 cells plays a key role in the inflammatory response in various diseases; the level of IL-17 production and Th17 cell development remained unchanged during the course of treatment. CD4+CD127lowCD25highFoxp3+ regulatory T cells (nTreg) play critical role in the suppression of excessive inflammatory response in various diseases including psoriasis. nTregs also regulate local and systemic immune response by maintaining the balance among Th1,Th2 and Th17/22 cells. The function of nTreg was also conserved during the course of treatment (Fig. 4). In addition, the cytokine production by CD8+ T cells and c/d T cells was similar between BTZ043 patients and controls (Fig. S2 and S3). In the present study, the skin manifestations of the patients markedly improved, despite unaltered cytokine production and T cell differentiation. The cytokine production and differentiation of T cells in response to infections and malignancies were preserved in the peripheral blood. On the other hand, the excessive production of inflammatory cytokines in the skin lesions was controlled during ustekinumab therapy. Evaluation of the qualitative alteration in T cell immunity during ustekinumab therapy is also important. Clonal expansion or loss of some T cell clones can be associated with risk of malignancy and infection. TCR BV subfamily immune-staining with TCR BV antibodies is a reliable tool for analysis of T cell receptor diversity; collapse and restoration of T cell receptor diversity was reported in CTCL patients in advanced stages of disease [23,30]. In the present study, no significant alteration in TCR diversity after ustekinumab therapy was observed, suggesting that ustekinumab has no effects on immunological competence (Fig. 5). In conclusion, the present data showed that ustekinumab improves clinical manifestations in patients with psoriasis without inducing immunosuppression. However, a study with a largerpopulation and longer follow-up should be carried out to confirm these observations.Supporting InformationFigure S1 The percentage of CD4+CD45RO+TNF-a+ T cells. The ratio of TNF-a producing memory CD4+ T cells was not suppressed in patients with psoriasis during ustekinumab treatment as compared to normal controls. (TIF)Cytokine production by memory CD8+ T cells. Flow cytometry data are shown. (A) The percentage of CD8a+IFN-c+ T cells (B) The percentage of CD8a+TNF-a+ T cells. The production of IFN-c and TNF-a by CD8+ T cells was not suppressed in patients with psoriasis treated with ustekinumab. (TIF)Figure S2 Figure S3 Cytokine production by c/d T cells. Flow cytometry data are shown. (A) The percentage of TCR c/d+IFNc+ T cells (B) The percentage of TCR c/d+IL-17+ T cells. The production of IFN-c and IL-17 from c/d T cells was not suppressed in patients with psoriasis treated with ustekinumab. (TIF)AcknowledgmentsThe authors thank Yuko Adachi for helpful technical assistance.Author ContributionsConceived and designed the experiments: KY HT HM. Performed the experiments: KT KY MK KM RS. Analyzed the data: KT KY. Wrote the paper: KT KY EG HM.
The genus Leishmania spp. 1454585-06-8 biological activity protozoa are pathogenic to a wide variety of hosts, including humans, and are most prevalent in tropical climates of developing countries. The major forms of leishmaniasis include cutaneous, mucosal and visceral leishmaniasis [1]. Leishmania (Leishmania) major is one the main etiological agents of CL in the Old World, while Leishmania.Unteer. doi:10.1371/journal.pone.0051819.gIL-17 secreted by Th17 cells plays a key role in the inflammatory response in various diseases; the level of IL-17 production and Th17 cell development remained unchanged during the course of treatment. CD4+CD127lowCD25highFoxp3+ regulatory T cells (nTreg) play critical role in the suppression of excessive inflammatory response in various diseases including psoriasis. nTregs also regulate local and systemic immune response by maintaining the balance among Th1,Th2 and Th17/22 cells. The function of nTreg was also conserved during the course of treatment (Fig. 4). In addition, the cytokine production by CD8+ T cells and c/d T cells was similar between patients and controls (Fig. S2 and S3). In the present study, the skin manifestations of the patients markedly improved, despite unaltered cytokine production and T cell differentiation. The cytokine production and differentiation of T cells in response to infections and malignancies were preserved in the peripheral blood. On the other hand, the excessive production of inflammatory cytokines in the skin lesions was controlled during ustekinumab therapy. Evaluation of the qualitative alteration in T cell immunity during ustekinumab therapy is also important. Clonal expansion or loss of some T cell clones can be associated with risk of malignancy and infection. TCR BV subfamily immune-staining with TCR BV antibodies is a reliable tool for analysis of T cell receptor diversity; collapse and restoration of T cell receptor diversity was reported in CTCL patients in advanced stages of disease [23,30]. In the present study, no significant alteration in TCR diversity after ustekinumab therapy was observed, suggesting that ustekinumab has no effects on immunological competence (Fig. 5). In conclusion, the present data showed that ustekinumab improves clinical manifestations in patients with psoriasis without inducing immunosuppression. However, a study with a largerpopulation and longer follow-up should be carried out to confirm these observations.Supporting InformationFigure S1 The percentage of CD4+CD45RO+TNF-a+ T cells. The ratio of TNF-a producing memory CD4+ T cells was not suppressed in patients with psoriasis during ustekinumab treatment as compared to normal controls. (TIF)Cytokine production by memory CD8+ T cells. Flow cytometry data are shown. (A) The percentage of CD8a+IFN-c+ T cells (B) The percentage of CD8a+TNF-a+ T cells. The production of IFN-c and TNF-a by CD8+ T cells was not suppressed in patients with psoriasis treated with ustekinumab. (TIF)Figure S2 Figure S3 Cytokine production by c/d T cells. Flow cytometry data are shown. (A) The percentage of TCR c/d+IFNc+ T cells (B) The percentage of TCR c/d+IL-17+ T cells. The production of IFN-c and IL-17 from c/d T cells was not suppressed in patients with psoriasis treated with ustekinumab. (TIF)AcknowledgmentsThe authors thank Yuko Adachi for helpful technical assistance.Author ContributionsConceived and designed the experiments: KY HT HM. Performed the experiments: KT KY MK KM RS. Analyzed the data: KT KY. Wrote the paper: KT KY EG HM.
The genus Leishmania spp. protozoa are pathogenic to a wide variety of hosts, including humans, and are most prevalent in tropical climates of developing countries. The major forms of leishmaniasis include cutaneous, mucosal and visceral leishmaniasis [1]. Leishmania (Leishmania) major is one the main etiological agents of CL in the Old World, while Leishmania.
