Anti-Programmed Cell Death 1 Antibody Reduces CD4+PD-1+ T Cells and Relieves the Lupus-Like Nephritis of NZB/W F1 Mice

Kasagi, Shimpei; Kawano, Seiji; Okazaki, Taku; Honjo, Tasuku; Morinobu, Akio; Hatachi, Saori; Shimatani, K.; Tanaka, Yoshimasa; Minato, Nagahiro; Kumagai, Shunichi

doi:10.4049/jimmunol.0901652

Cited by 74 publications

(55 citation statements)

References 46 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In either case, these results strongly suggest that CD153 + PD-1 + CD4 + T cells capable of producing OPN play a crucial, if not sufficient, role in lupus pathogenesis; development of clinical lupus disease in f-BWF1 mice certainly requires other immune cell disorders, including B cells (11). The conclusion is consistent with our previous report that administration of anti-PD-1 Ab, but not anti-PD-L1 Ab, ameliorates the lethal lupus disease in f-BWF1 mice via cell-ablative effect on PD-1 + CD4 + T cells (41). Thus, CD153 + TF cells per se or OPN secreted by them may be a potential therapeutic target for controlling human SLE.…”

Section: Discussionsupporting

confidence: 81%

A CD153+CD4+ T Follicular Cell Population with Cell-Senescence Features Plays a Crucial Role in Lupus Pathogenesis via Osteopontin Production

Tahir

Fukushima

Sakamoto

et al. 2015

The Journal of Immunology

Self Cite

118

View full text Add to dashboard Cite

Immune aging results in diminished adaptive immunity and increased risk for autoimmunity. We previously reported a unique PD-1+ CD44highCD4+ T cell population that increases with age in normal mice. In this study, we indicate that the age-dependent PD-1+ CD44highCD4+ T cells develop as unique T follicular (TF) cells in a B cell–dependent manner and consist of two subpopulations, as follows: CD153+ cells preferentially secreting abundant osteopontin on TCR stimulation and CD153− cells that are apparently TCR anergic. These unique TF cells with essentially similar features increase much earlier and are accumulated in the spontaneous germinal centers (GCs) in lupus-prone female BWF1 (f-BWF1) mice. These TF cells showed characteristic cell-senescence features and developed in association with extensive CD4+ T cell proliferation in vivo, suggesting replicative senescence. Although the CD153+ TF cells were defective in proliferation capacity, they were quite stable and specifically responded to self GC-B cells to secret abundant osteopontin, which inhibited B cell receptor–induced GC-B cell apoptosis in f-BWF1 mice. Transfer of CD153+ PD-1+ CD4+ T cells promoted the growth of spontaneous GCs, whereas administration of anti-osteopontin Ab suppressed GC enlargement and anti-nuclear Ab production and ameliorated clinical lupus nephritis of f-BWF1 mice. Current results suggest that senescent CD153+ TF cells generated as a consequence of extensive endogenous CD4+ T cell proliferation play an essential, if not sufficient, role in lupus pathogenesis in lupus-prone genetic background and may also contribute to an increased autoimmunity risk with age.

show abstract

Section: Discussionsupporting

confidence: 81%

A CD153+CD4+ T Follicular Cell Population with Cell-Senescence Features Plays a Crucial Role in Lupus Pathogenesis via Osteopontin Production

Tahir

Fukushima

Sakamoto

et al. 2015

The Journal of Immunology

Self Cite

118

View full text Add to dashboard Cite

show abstract

“…The expansion following anti-PD-1 mAb was significant relative to control mice. A recent study using the same anti-PD-1 clone (J43) used in this study found that the Ab increased complement-dependent cell death in PD-1 + T cells, which may explain the reduced T FH cell expansion compared with that induced by anti-B7-H1 (32). Alternatively, CD80 has also been described as a ligand for B7-H1 (33).…”

Section: In Vivo Blocking Of B7-h1 But Not B7-dc Expands T Fh Cellsmentioning

confidence: 73%

“…Indeed, a recent study demonstrated that PD-1 blockade evoked a 2-to 8-fold increase in the SIV-specific Ab titer in a macaque model of HIV with improved survival (44). Conversely, in vivo blockade with anti-B7-H1 enhanced IgG2a in a murine model of systemic lupus erythematosous, leading to accelerated nephritis and increased mortality (32). In this article we provide evidence for an in vivo cellular mechanism that explains previous observations of adverse outcome, whereby modulation of the PD-1/B7-H1 signaling pathway will alter Ig production through regulation of T FH cell expansion.…”

Section: Discussionmentioning

confidence: 99%

Blockade of B7-H1 (Programmed Death Ligand 1) Enhances Humoral Immunity by Positively Regulating the Generation of T Follicular Helper Cells

Hams

McCarron

Amu

et al. 2011

The Journal of Immunology

118

115

View full text Add to dashboard Cite

T follicular helper (TFH) cells are critical initiators in the development of T cell-dependent humoral immunity and the generation of protective immunity. We demonstrate that TFH cell accumulation and Ab production are negatively regulated by B7-H1 (programmed death ligand 1) in response to both helminth infection and active immunization. Following immunization of B7-H1−/− mice with keyhole limpet hemocyanin or helminth Ags, there is a profound increase in induction of TFH cells as a result of increased cell cycling and decreased apoptosis relative to wild-type mice. The increase in TFH cells in the absence of B7-H1 was associated with significant elevations in Ag-specific Ig response. Cotransfer experiments in vivo demonstrated that B7-H1 expression on B cells was required for negatively regulating TFH cell expansion and production of Ag-specific Ig. Treatment of immunized wild-type mice with anti–B7-H1 or anti-programmed death 1 mAbs, but not anti–B7-DC, led to a significant expansion of the TFH cell population and an enhanced Ag-specific Ig response. Our results demonstrate that the coinhibitory B7-H1/programmed death 1 pathway can limit the expansion of TFH cells and constrain Ag-specific Ig responses. This finding has direct implications for investigations examining the feasibility of therapeutically manipulating this pathway and reveals new insights into the regulation of the humoral immune response.

show abstract

“…5 Blockade of PD-1 has been shown to affect disease severity in a mouse model of lupus. 6 Moreover, lower PD-1 receptor expression on CD4 T cells was observed in SLE patients, and several polymorphisms of the PD-1.3 allele are associated with this disease. [7][8][9] We have recently demonstrated an impaired response of peripheral cells to TGF-b1 in patients with active SLE.…”

mentioning

confidence: 99%

PD-1 induction through TCR activation is partially regulated by endogenous TGF-β

et al. 2014

View full text Add to dashboard Cite

The programmed death 1 (PD-1) pathway is a way of inhibiting T-cell proliferation and cytokine production. This pathway is important for maintaining peripheral tolerance. Different mechanisms and cytokines are involved in this pathway. Herein, we show the contribution of endogenous TGF-b to increasing PD-1 expression after T cell receptor (TCR) activation.The receptor for PD-1, also called CD279, is a regulatory protein of the CD28 family and is expressed at low levels on the surface of resting T and B lymphocytes.1 PD-1 is induced by the expression of TCR or B-cell receptor signaling.2 Its induction on the surface of activated T cells can prevent a runaway immune response. Indeed, the interaction between PD-1 and its ligand (PD-L1 or PD-L2) inhibits proliferation and effector functions of T cells and induces apoptosis.

show abstract

Anti-Programmed Cell Death 1 Antibody Reduces CD4+PD-1+ T Cells and Relieves the Lupus-Like Nephritis of NZB/W F1 Mice

Abstract: Material

Cited by 74 publications

References 46 publications

A CD153+CD4+ T Follicular Cell Population with Cell-Senescence Features Plays a Crucial Role in Lupus Pathogenesis via Osteopontin Production

A CD153+CD4+ T Follicular Cell Population with Cell-Senescence Features Plays a Crucial Role in Lupus Pathogenesis via Osteopontin Production

Blockade of B7-H1 (Programmed Death Ligand 1) Enhances Humoral Immunity by Positively Regulating the Generation of T Follicular Helper Cells

PD-1 induction through TCR activation is partially regulated by endogenous TGF-β

Contact Info

Product

Resources

About