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Santi Suryani

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Papers by Santi Suryani

Research paper thumbnail of An interferon-γ-producing Th1 subset is the major source of IL17 in experimental autoimmune encephalitis

Journal of Neuroimmunology, 2007

ThIL-17 (IL-17+/IFN-gamma-) cell lines are significantly more encephalitogenic than Th1 (IL-17-/I... more ThIL-17 (IL-17+/IFN-gamma-) cell lines are significantly more encephalitogenic than Th1 (IL-17-/IFN-gamma+) cell lines in adoptive transfer EAE models. In actively induced EAE short ex vivo peptide stimulation identifies an IL-17+/IFN-gamma+ population of CD4+ CNS-infiltrating MOG35-55-specific T cells, which outnumber IL-17+/IFN-gamma- cells by approximately 3:1 as disease develops. A decrease in numbers of IL-17+/IFN-gamma+ cells following in vitro culture is accompanied by an increase in IL-17-/IFN-gamma+ cell numbers. Together these ex vivo and in vitro observations imply that the Th1 lineage is more encephalitogenic than is suggested by adoptive transfer of Th1 (IL-17-/IFN-gamma+) cell lines which have been terminally differentiated in vitro.

Research paper thumbnail of Early commitment of naïve human CD4+ T cells to the T follicular helper (TFH) cell lineage is induced by IL12

Immunology and Cell Biology, 2009

T follicular helper (T FH ) cells are a specialized subset of CD4 + T cells that localize to B-ce... more T follicular helper (T FH ) cells are a specialized subset of CD4 + T cells that localize to B-cell follicles, where they are positioned to provide help for the induction of optimal humoral immune responses. Key features of T FH cells are the expressions of CXCR5, ICOS, interleukin (IL)-21 and BCL-6. The requirements for human T FH cell development are unknown. Here we show that IL-6, IL-12, IL-21 and IL-23 are capable of inducing IL-21 expression in naïve CD4 + T cells isolated from human tonsils, peripheral blood and cord blood. However, only IL-12 induced sustained expressions of CXCR5 and ICOS on these activated naïve CD4 + T cells, and endowed them with the ability to provide increased help to B cells for their differentiation into immunoglobulinsecreting cells. The effects of IL-12 were independent of interferon-c and T-bet, and associated with upregulation of BCL-6 expression. Thus, these cytokines, particularly IL-12, are likely to act at an early stage during dendritic cell-mediated priming of naïve CD4 + T cells into a T FH cell fate, and thus underpin antibody-mediated immunity.

Research paper thumbnail of Differential expression of CD21 identifies developmentally and functionally distinct subsets of human transitional B cells

Blood, 2010

The transitional stage of B-cell development represents an important step where autoreactive cell... more The transitional stage of B-cell development represents an important step where autoreactive cells are deleted, allowing the generation of a mature functional B-cell repertoire. In mice, 3 subsets of transitional B cells have been identified. In contrast, most studies of human transitional B cells have focused on a single subset defined as CD24 hi CD38 hi B cells. Here, we have identified 2 subsets of human transitional B cells based on the differential expression of CD21. CD21 hi transitional cells displayed higher expres-sion of CD23, CD44, and IgD, and exhibited greater proliferation and Ig secretion in vitro than CD21 lo transitional B cells. In contrast, the CD21 lo subset expressed elevated levels of LEF1, a transcription factor highly expressed by immature lymphocytes, and produced higher amounts of autoreactive Ab. These phenotypic, functional, and molecular features suggest that CD21 lo transitional B cells are less mature than the CD21 hi subset. This was confirmed by analyzing X-linked agammaglobulinemia patients and the ki-netics of B-cell reconstitution after stem cell transplantation, which revealed that the development of CD21 lo transitional B cells preceded that of CD21 hi transitional cells. These findings provide important insights into the process of human B-cell development and have implications for understanding the processes underlying perturbed B-cell maturation in autoimmune and immunodeficient conditions. (Blood. 2010;115:519-529)

Research paper thumbnail of An interferon-γ-producing Th1 subset is the major source of IL17 in experimental autoimmune encephalitis

Journal of Neuroimmunology, 2007

ThIL-17 (IL-17+/IFN-gamma-) cell lines are significantly more encephalitogenic than Th1 (IL-17-/I... more ThIL-17 (IL-17+/IFN-gamma-) cell lines are significantly more encephalitogenic than Th1 (IL-17-/IFN-gamma+) cell lines in adoptive transfer EAE models. In actively induced EAE short ex vivo peptide stimulation identifies an IL-17+/IFN-gamma+ population of CD4+ CNS-infiltrating MOG35-55-specific T cells, which outnumber IL-17+/IFN-gamma- cells by approximately 3:1 as disease develops. A decrease in numbers of IL-17+/IFN-gamma+ cells following in vitro culture is accompanied by an increase in IL-17-/IFN-gamma+ cell numbers. Together these ex vivo and in vitro observations imply that the Th1 lineage is more encephalitogenic than is suggested by adoptive transfer of Th1 (IL-17-/IFN-gamma+) cell lines which have been terminally differentiated in vitro.

Research paper thumbnail of Early commitment of naïve human CD4+ T cells to the T follicular helper (TFH) cell lineage is induced by IL12

Immunology and Cell Biology, 2009

T follicular helper (T FH ) cells are a specialized subset of CD4 + T cells that localize to B-ce... more T follicular helper (T FH ) cells are a specialized subset of CD4 + T cells that localize to B-cell follicles, where they are positioned to provide help for the induction of optimal humoral immune responses. Key features of T FH cells are the expressions of CXCR5, ICOS, interleukin (IL)-21 and BCL-6. The requirements for human T FH cell development are unknown. Here we show that IL-6, IL-12, IL-21 and IL-23 are capable of inducing IL-21 expression in naïve CD4 + T cells isolated from human tonsils, peripheral blood and cord blood. However, only IL-12 induced sustained expressions of CXCR5 and ICOS on these activated naïve CD4 + T cells, and endowed them with the ability to provide increased help to B cells for their differentiation into immunoglobulinsecreting cells. The effects of IL-12 were independent of interferon-c and T-bet, and associated with upregulation of BCL-6 expression. Thus, these cytokines, particularly IL-12, are likely to act at an early stage during dendritic cell-mediated priming of naïve CD4 + T cells into a T FH cell fate, and thus underpin antibody-mediated immunity.

Research paper thumbnail of Differential expression of CD21 identifies developmentally and functionally distinct subsets of human transitional B cells

Blood, 2010

The transitional stage of B-cell development represents an important step where autoreactive cell... more The transitional stage of B-cell development represents an important step where autoreactive cells are deleted, allowing the generation of a mature functional B-cell repertoire. In mice, 3 subsets of transitional B cells have been identified. In contrast, most studies of human transitional B cells have focused on a single subset defined as CD24 hi CD38 hi B cells. Here, we have identified 2 subsets of human transitional B cells based on the differential expression of CD21. CD21 hi transitional cells displayed higher expres-sion of CD23, CD44, and IgD, and exhibited greater proliferation and Ig secretion in vitro than CD21 lo transitional B cells. In contrast, the CD21 lo subset expressed elevated levels of LEF1, a transcription factor highly expressed by immature lymphocytes, and produced higher amounts of autoreactive Ab. These phenotypic, functional, and molecular features suggest that CD21 lo transitional B cells are less mature than the CD21 hi subset. This was confirmed by analyzing X-linked agammaglobulinemia patients and the ki-netics of B-cell reconstitution after stem cell transplantation, which revealed that the development of CD21 lo transitional B cells preceded that of CD21 hi transitional cells. These findings provide important insights into the process of human B-cell development and have implications for understanding the processes underlying perturbed B-cell maturation in autoimmune and immunodeficient conditions. (Blood. 2010;115:519-529)

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