Regulation of Follicular Dendritic Cell Networks by Activated T Cells: The Role of CD137 Signaling

Sun, Yonglian; Blink, Sarah E.; Chen, Jonathan; Fu, Yang Xin

doi:10.4049/jimmunol.175.2.884

Cited by 27 publications

(29 citation statements)

References 38 publications

(44 reference statements)

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“…B cell loss was not seen in the NZB × NZW F1 strain, but, germinal center (GC) formation, which is central to the development of functional classswitched B cells, was abolished. In accordance with the latter, a recent report also showed that anti-4-1BB inhibited GC formation apparently by diminishing follicular dendritic cell (FDC) networks in B cell follicles [62]. Whether this activity was direct or indirect via another cell type is not clear, but it is possible that again suppression of B cell immunity was accompanied by enhanced CD8 responses.…”

Section: Cd8+ Treg and Novel Immune Regulation From 4-1bbmentioning

confidence: 60%

Immune regulation and control of regulatory T cells by OX40 and 4-1BB

Lee

Croft

2008

Cytokine & Growth Factor Reviews

120

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The TNFR family members OX40 (CD134) and 4-1BB (CD137) have been found to play major roles as costimulatory receptors for both CD4 and CD8 T cells. In particular, in many situations, they can control proliferation, survival, and cytokine production, and hence are thought to dictate accumulation of protective T cells during anti-viral and anti-tumor responses and pathogenic T cells during autoimmune reactions. As opposed to simply controlling the activity of naïve, effector, and memory T cells, recent data have suggested that both molecules are also instrumental in controlling the generation and activity of so-called regulatory or suppressor T cells (Treg), perhaps in both positive and negative manners. Part of the action on Treg might function to further promote protective or pathogenic T cells, but alternate activities of OX40 and 4-1BB on Treg are also being described that suggest there might be control by these molecules at multiple levels that will alter the biological outcome when these receptors are ligated. This review specifically focuses on recent studies of regulatory T cells, and regulatory or suppressive activity, that are modulated by OX40 or 4-1BB.

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Section: Cd8+ Treg and Novel Immune Regulation From 4-1bbmentioning

confidence: 60%

Immune regulation and control of regulatory T cells by OX40 and 4-1BB

Lee

Croft

2008

Cytokine & Growth Factor Reviews

120

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“…Indeed, in contrast to OX40L, CD70-driven costimulation resulted in down-regulation of GCs and Ab responses. 4-1BBL promoted infiltration of B cell follicles by CD4 and CD8 T cells as well, and this also triggered inhibition of T cell-dependent humoral responses (59,60). In contrast to CD70, 4-1BBL down-regulated Ab production through CD4 and CD8 T cell-mediated destruction of follicular dendritic cell networks in B cell follicles rather than through a GC B celldependent pathway (60).…”

Section: Discussionmentioning

confidence: 99%

Chronic CD70-Driven Costimulation Impairs IgG Responses by Instructing T Cells to Inhibit Germinal Center B Cell Formation through FasL-Fas Interactions

Beishuizen

Kragten

Boon³

et al. 2009

The Journal of Immunology

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CD70 provides costimulation that enhances effector T cell differentiation upon binding of its receptor, CD27. During chronic immune activation, CD70 is constitutively expressed on activated immune cells, and this induces T cell-driven disruption of neutralizing Ab responses via an unknown mechanism. We used CD70-transgenic mice to investigate the effect of constitutive expression of CD70 on T cell-dependent B cell responses. CD70 induced up-regulation of the B cell follicle homing chemokine receptor CXCR5 on T cells, enabling not only CD4 but also CD8 T cells to infiltrate the B cell follicles. CD70-transgenic mice failed to develop productive germinal center formation and displayed impaired IgG Ab responses. Defective germinal center B cell differentiation was critically dependent on CD70-mediated CD27 signaling in T cells, and involved Fas-dependent impairment of germinal center B cell differentiation. Thus, CD70-driven costimulation enables T cells to terminate B cell responses, thereby compromising durable Ab production. Our findings imply that the CD70- and CD27-driven costimulatory axis may be involved in shutdown of B cell responses before clearance of Ag. Because CD70 is expressed constitutively in chronic viral infections such as HIV-1 infection, this mechanism may also contribute to defects in humoral immunity associated with this disease.

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“…Several studies have shown that agonist Abs to 4-1BB can be highly suppressive for humoral responses (28,29) and for a number of autoimmune responses (30 -34). Also, other data have now shown enhanced responses in 4-1BB-deficient animals (35,36).…”

Section: Functional Dichotomy Between Ox40 and 4-1bb Inmentioning

confidence: 99%

Functional Dichotomy between OX40 and 4-1BB in Modulating Effector CD8 T Cell Responses

Lee

Park

Song

et al. 2006

The Journal of Immunology

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Members of the TNFR family are thought to deliver costimulatory signals to T cells and modulate their function and survival. In this study, we compare the role of two closely related TNFR family molecules, OX40 and 4-1BB, in generating effector CD8 T cells to Ag delivered by adenovirus. OX40 and 4-1BB were both induced on responding naive CD8 T cells, but 4-1BB exhibited faster and more sustained kinetics than OX40. OX40-deficient CD8 T cells initially expanded normally; however, their accumulation and survival at late times in the primary response was significantly impaired. In contrast, 4-1BB-deficient CD8 T cells displayed hyperresponsiveness, expanding more than wild-type cells. The 4-1BB-deficient CD8 T cells also showed enhanced maturation attributes, whereas OX40-deficient CD8 T cells had multiple defects in the expression of effector cell surface markers, the synthesis of cytokines, and in cytotoxic activity. These results suggest that, in contrast to current ideas, OX40 and 4-1BB can have a clear functional dichotomy in modulating effector CD8 T cell responses. OX40 can positively regulate effector function and late accumulation/survival, whereas 4-1BB can initially operate in a negative manner to limit primary CD8 responses.

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Regulation of Follicular Dendritic Cell Networks by Activated T Cells: The Role of CD137 Signaling

Cited by 27 publications

References 38 publications

Immune regulation and control of regulatory T cells by OX40 and 4-1BB

Immune regulation and control of regulatory T cells by OX40 and 4-1BB

Chronic CD70-Driven Costimulation Impairs IgG Responses by Instructing T Cells to Inhibit Germinal Center B Cell Formation through FasL-Fas Interactions

Functional Dichotomy between OX40 and 4-1BB in Modulating Effector CD8 T Cell Responses

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