FcRγ controls the fas-dependent regulatory function of lymphoproliferative double negative T cells.
Patients with autoimmune lymphoproliferative syndrome (ALPS) and lymphoproliferation (LPR) mice are deficient in Fas, and accumulate large numbers of αβ-TCR(+), CD4(-), CD8(-) double negative (DN) T cells. The function of these DN T cells remains largely unknown. The common γ subunit of the activati...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3675138?pdf=render |
| _version_ | 1819074384663412736 |
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| author | Stephen C Juvet Christopher W Thomson Edward Y Kim Mei Han Li Zhang |
| author_facet | Stephen C Juvet Christopher W Thomson Edward Y Kim Mei Han Li Zhang |
| author_sort | Stephen C Juvet |
| collection | DOAJ |
| description | Patients with autoimmune lymphoproliferative syndrome (ALPS) and lymphoproliferation (LPR) mice are deficient in Fas, and accumulate large numbers of αβ-TCR(+), CD4(-), CD8(-) double negative (DN) T cells. The function of these DN T cells remains largely unknown. The common γ subunit of the activating Fc receptors, FcRγ, plays an important role in mediating innate immune responses. We have shown previously that a significant proportion of DN T cells express FcRγ, and that this molecule is required for TCR transgenic DN T cells to suppress allogeneic immune responses. Whether FcRγ plays a critical role in LPR DN T cell-mediated suppression of immune responses to auto and allo-antigens is not known. Here, we demonstrated that FcRγ(+), but not FcRγ(-) LPR DN T cells could suppress Fas(+) CD4(+) and CD8(+) T cell proliferation in vitro and attenuated CD4(+) T cell-mediated graft-versus host disease. Although FcRγ expression did not allow LPR DN T cells to inhibit the expansion of Fas-deficient cells within the LPR context, adoptive transfer of FcRγ(+), but not FcRγ(-), DN T cells inhibited lymphoproliferation in generalized lymphoproliferative disease (GLD) mice. Furthermore, FcRγ acted in a cell-intrinsic fashion to limit DN T cell accumulation by increasing the rate of apoptosis in proliferated cells. These results indicate that FcRγ can confer Fas-dependent regulatory properties on LPR DN T cells, and suggest that FcRγ may be a novel marker for functional DN Tregs. |
| first_indexed | 2024-12-21T18:08:40Z |
| format | Article |
| id | doaj.art-6f8e354bbcf04da6bb81d32f15bd4dc8 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T18:08:40Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6f8e354bbcf04da6bb81d32f15bd4dc82022-12-21T18:54:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6525310.1371/journal.pone.0065253FcRγ controls the fas-dependent regulatory function of lymphoproliferative double negative T cells.Stephen C JuvetChristopher W ThomsonEdward Y KimMei HanLi ZhangPatients with autoimmune lymphoproliferative syndrome (ALPS) and lymphoproliferation (LPR) mice are deficient in Fas, and accumulate large numbers of αβ-TCR(+), CD4(-), CD8(-) double negative (DN) T cells. The function of these DN T cells remains largely unknown. The common γ subunit of the activating Fc receptors, FcRγ, plays an important role in mediating innate immune responses. We have shown previously that a significant proportion of DN T cells express FcRγ, and that this molecule is required for TCR transgenic DN T cells to suppress allogeneic immune responses. Whether FcRγ plays a critical role in LPR DN T cell-mediated suppression of immune responses to auto and allo-antigens is not known. Here, we demonstrated that FcRγ(+), but not FcRγ(-) LPR DN T cells could suppress Fas(+) CD4(+) and CD8(+) T cell proliferation in vitro and attenuated CD4(+) T cell-mediated graft-versus host disease. Although FcRγ expression did not allow LPR DN T cells to inhibit the expansion of Fas-deficient cells within the LPR context, adoptive transfer of FcRγ(+), but not FcRγ(-), DN T cells inhibited lymphoproliferation in generalized lymphoproliferative disease (GLD) mice. Furthermore, FcRγ acted in a cell-intrinsic fashion to limit DN T cell accumulation by increasing the rate of apoptosis in proliferated cells. These results indicate that FcRγ can confer Fas-dependent regulatory properties on LPR DN T cells, and suggest that FcRγ may be a novel marker for functional DN Tregs.http://europepmc.org/articles/PMC3675138?pdf=render |
| spellingShingle | Stephen C Juvet Christopher W Thomson Edward Y Kim Mei Han Li Zhang FcRγ controls the fas-dependent regulatory function of lymphoproliferative double negative T cells. PLoS ONE |
| title | FcRγ controls the fas-dependent regulatory function of lymphoproliferative double negative T cells. |
| title_full | FcRγ controls the fas-dependent regulatory function of lymphoproliferative double negative T cells. |
| title_fullStr | FcRγ controls the fas-dependent regulatory function of lymphoproliferative double negative T cells. |
| title_full_unstemmed | FcRγ controls the fas-dependent regulatory function of lymphoproliferative double negative T cells. |
| title_short | FcRγ controls the fas-dependent regulatory function of lymphoproliferative double negative T cells. |
| title_sort | fcrγ controls the fas dependent regulatory function of lymphoproliferative double negative t cells |
| url | http://europepmc.org/articles/PMC3675138?pdf=render |
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