Limits...
Agonistic Anti-CD137 Monoclonal Antibody Treatment Induces CD11bGr-1 Myeloid-derived Suppressor Cells.

Lee JM, Seo JH, Kim YJ, Kim YS, Ko HJ, Kang CY - Immune Netw (2010)

Bottom Line: Intriguingly, anti-CD137 mAb injection significantly increased CD11b(+)Gr-1(+) cells, peaking at days 5 to 10 and continuing for at least 25 days.Furthermore, this cell population could suppress both CD8(+) T cells and CD4(+) T cells.Thus, this study demonstrated that, for the first time, anti-CD137 mAb treatment could induce CD11b(+)Gr-1(+) MDSCs under normal conditions, suggesting a possible relationship between myeloid cell induction and CD137-mediated immune suppression.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunology, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.

ABSTRACT
CD137 (4-1BB/tnfrsf9) has been shown to co-stimulate T cells. However, agonistic anti-CD137 monoclonal antibody (mAb) treatment can suppress CD4(+) T cells, ameliorating autoimmune diseases, whereas it induces activation of CD8(+) T cells, resulting in diverse therapeutic activity in cancer, viral infection. To investigate the CD137-mediated T cell suppression mechanism, we examined whether anti-CD137 mAb treatment could affect CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs). Intriguingly, anti-CD137 mAb injection significantly increased CD11b(+)Gr-1(+) cells, peaking at days 5 to 10 and continuing for at least 25 days. Furthermore, this cell population could suppress both CD8(+) T cells and CD4(+) T cells. Thus, this study demonstrated that, for the first time, anti-CD137 mAb treatment could induce CD11b(+)Gr-1(+) MDSCs under normal conditions, suggesting a possible relationship between myeloid cell induction and CD137-mediated immune suppression.

No MeSH data available.


Related in: MedlinePlus

Increased xCD11b+Gr-1+ cells by CD137 stimulation suppress T cell proliferation. Total splenocytes (4×105) of DO11.10 mice (A, C) or OT-I mice (B, D) were stimulated with OVA protein (A, C: 100µg/ml, B, D: 250µg/ml) and serially diluted naïve splenic CD11b+Gr-1+ cells or 3H3 induced CD11b+Gr-1+ cells (A, B: 5 days after 3H3 treatment; C, D: 25 days after 3H3 treatment) were added. Three days after culture, T cell proliferation was examined including an 18 hr pulse with 4µCi/ml [3H] thymidine.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2902672&req=5

Figure 3: Increased xCD11b+Gr-1+ cells by CD137 stimulation suppress T cell proliferation. Total splenocytes (4×105) of DO11.10 mice (A, C) or OT-I mice (B, D) were stimulated with OVA protein (A, C: 100µg/ml, B, D: 250µg/ml) and serially diluted naïve splenic CD11b+Gr-1+ cells or 3H3 induced CD11b+Gr-1+ cells (A, B: 5 days after 3H3 treatment; C, D: 25 days after 3H3 treatment) were added. Three days after culture, T cell proliferation was examined including an 18 hr pulse with 4µCi/ml [3H] thymidine.

Mentions: Next, to investigate that the CD11b+Gr-1+ cells induced by anti-CD137 mAb treatment had suppressive activity similar to MDSCs, the effect of CD137 stimulation-induced CD11b+Gr-1+ cells on Ag-specific T cell proliferation was tested. As a result, OVA Ag-specific proliferation of DO11.10 splenocytes and OT-I splenocytes was down-regulated in a dose-dependent manner by CD11b+Gr-1+ cells isolated at 5 day after anti-CD137 mAb treatment, as compared to CD11b+Gr-1+ cells obtained from naïve mice (Fig. 3A and B). Furthermore, this suppressive activity was also shown in CD11b+Gr-1+ cells isolated at 25 day after anti-CD137 mAb injection (Fig. 3C and D). Collectively, we concluded that CD137 stimulation dramatically induced CD11b+Gr-1+ cells, which suppressed both CD8+ and CD4+ T cells.


Agonistic Anti-CD137 Monoclonal Antibody Treatment Induces CD11bGr-1 Myeloid-derived Suppressor Cells.

Lee JM, Seo JH, Kim YJ, Kim YS, Ko HJ, Kang CY - Immune Netw (2010)

Increased xCD11b+Gr-1+ cells by CD137 stimulation suppress T cell proliferation. Total splenocytes (4×105) of DO11.10 mice (A, C) or OT-I mice (B, D) were stimulated with OVA protein (A, C: 100µg/ml, B, D: 250µg/ml) and serially diluted naïve splenic CD11b+Gr-1+ cells or 3H3 induced CD11b+Gr-1+ cells (A, B: 5 days after 3H3 treatment; C, D: 25 days after 3H3 treatment) were added. Three days after culture, T cell proliferation was examined including an 18 hr pulse with 4µCi/ml [3H] thymidine.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2902672&req=5

Figure 3: Increased xCD11b+Gr-1+ cells by CD137 stimulation suppress T cell proliferation. Total splenocytes (4×105) of DO11.10 mice (A, C) or OT-I mice (B, D) were stimulated with OVA protein (A, C: 100µg/ml, B, D: 250µg/ml) and serially diluted naïve splenic CD11b+Gr-1+ cells or 3H3 induced CD11b+Gr-1+ cells (A, B: 5 days after 3H3 treatment; C, D: 25 days after 3H3 treatment) were added. Three days after culture, T cell proliferation was examined including an 18 hr pulse with 4µCi/ml [3H] thymidine.
Mentions: Next, to investigate that the CD11b+Gr-1+ cells induced by anti-CD137 mAb treatment had suppressive activity similar to MDSCs, the effect of CD137 stimulation-induced CD11b+Gr-1+ cells on Ag-specific T cell proliferation was tested. As a result, OVA Ag-specific proliferation of DO11.10 splenocytes and OT-I splenocytes was down-regulated in a dose-dependent manner by CD11b+Gr-1+ cells isolated at 5 day after anti-CD137 mAb treatment, as compared to CD11b+Gr-1+ cells obtained from naïve mice (Fig. 3A and B). Furthermore, this suppressive activity was also shown in CD11b+Gr-1+ cells isolated at 25 day after anti-CD137 mAb injection (Fig. 3C and D). Collectively, we concluded that CD137 stimulation dramatically induced CD11b+Gr-1+ cells, which suppressed both CD8+ and CD4+ T cells.

Bottom Line: Intriguingly, anti-CD137 mAb injection significantly increased CD11b(+)Gr-1(+) cells, peaking at days 5 to 10 and continuing for at least 25 days.Furthermore, this cell population could suppress both CD8(+) T cells and CD4(+) T cells.Thus, this study demonstrated that, for the first time, anti-CD137 mAb treatment could induce CD11b(+)Gr-1(+) MDSCs under normal conditions, suggesting a possible relationship between myeloid cell induction and CD137-mediated immune suppression.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunology, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea.

ABSTRACT
CD137 (4-1BB/tnfrsf9) has been shown to co-stimulate T cells. However, agonistic anti-CD137 monoclonal antibody (mAb) treatment can suppress CD4(+) T cells, ameliorating autoimmune diseases, whereas it induces activation of CD8(+) T cells, resulting in diverse therapeutic activity in cancer, viral infection. To investigate the CD137-mediated T cell suppression mechanism, we examined whether anti-CD137 mAb treatment could affect CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs). Intriguingly, anti-CD137 mAb injection significantly increased CD11b(+)Gr-1(+) cells, peaking at days 5 to 10 and continuing for at least 25 days. Furthermore, this cell population could suppress both CD8(+) T cells and CD4(+) T cells. Thus, this study demonstrated that, for the first time, anti-CD137 mAb treatment could induce CD11b(+)Gr-1(+) MDSCs under normal conditions, suggesting a possible relationship between myeloid cell induction and CD137-mediated immune suppression.

No MeSH data available.


Related in: MedlinePlus