Human CD8+HLA-DR+ Regulatory T Cells, Similarly to Classical CD4+Foxp3+ Cells, Suppress Immune Responses via PD-1/PD-L1 Axis
We have previously identified a human CD8+HLA-DR+ regulatory T cell subset with the ability to suppress proliferation of autologous PBMCs responder cells through cell contact and CTLA-4 co-inhibitory molecule. The present study characterizes the complete phenotype of CD8+HLA-DR+ Treg cells which sho...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02788/full |
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| author | Andres Machicote Santiago Belén Placida Baz Luis A. Billordo Leonardo Fainboim Leonardo Fainboim |
| author_facet | Andres Machicote Santiago Belén Placida Baz Luis A. Billordo Leonardo Fainboim Leonardo Fainboim |
| author_sort | Andres Machicote |
| collection | DOAJ |
| description | We have previously identified a human CD8+HLA-DR+ regulatory T cell subset with the ability to suppress proliferation of autologous PBMCs responder cells through cell contact and CTLA-4 co-inhibitory molecule. The present study characterizes the complete phenotype of CD8+HLA-DR+ Treg cells which showed great similarities with classical CD4+ cells expressing forkhead box P3 (FOXP3). The shared features included the expression of programmed cell death protein 1 (PD-1), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), C-C chemokine receptor type 4 and 5 (CCR4 and CCR5), low expression of CD127, and a memory and effector-like phenotype. CD8+HLA-DR+ Treg-induced suppression on CD8+ responder T cells was abrogated by an anti-PD1 neutralizing antibody. Anti-PD-1 did not abrogate the suppressor effect induced on responder CD4+ T cells. In addition, CD8+HLA-DR+ Treg induced a preferential death on responder CD8+ T cells. This effect was not reversed by PD-1 neutralization. After activation, most CD8+HLA-DR+ Treg acquire programmed death-ligand 1 (PD-L1) expression. Interestingly, PD-L1 may induce apoptosis through CD80 expressed on activated CD8+ responder T cells. After PBMCs stimulation, CD8+HLA-DR+ Treg cells showed an increased frequency of IFN-γ and TNFα positive cells and higher degranulation. These data strongly argue against CD8+HLA-DR+ Treg being exhausted cells. Overall, the data presented in this study indicate that CD8+HLA-DR+ Treg and CD4+FOXP3+ Treg share phenotypic and functional features, which may provide cues to similar involvements in the control of antitumor immune responses and autoimmunity. |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T01:35:44Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-a7b12fc3fc7a42a7a2bec92c118b3e4e2022-12-22T00:42:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-11-01910.3389/fimmu.2018.02788385652Human CD8+HLA-DR+ Regulatory T Cells, Similarly to Classical CD4+Foxp3+ Cells, Suppress Immune Responses via PD-1/PD-L1 AxisAndres Machicote0Santiago Belén1Placida Baz2Luis A. Billordo3Leonardo Fainboim4Leonardo Fainboim5Laboratorio de Inmunogenética, Facultad de Farmacia y Bioquímica, Instituto de Inmunología, Genética y Metabolismo, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, ArgentinaLaboratorio de Inmunogenética, Facultad de Farmacia y Bioquímica, Instituto de Inmunología, Genética y Metabolismo, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, ArgentinaLaboratorio de Inmunogenética, Facultad de Farmacia y Bioquímica, Instituto de Inmunología, Genética y Metabolismo, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, ArgentinaLaboratorio de Inmunogenética, Facultad de Farmacia y Bioquímica, Instituto de Inmunología, Genética y Metabolismo, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, ArgentinaLaboratorio de Inmunogenética, Facultad de Farmacia y Bioquímica, Instituto de Inmunología, Genética y Metabolismo, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, ArgentinaDepartamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, ArgentinaWe have previously identified a human CD8+HLA-DR+ regulatory T cell subset with the ability to suppress proliferation of autologous PBMCs responder cells through cell contact and CTLA-4 co-inhibitory molecule. The present study characterizes the complete phenotype of CD8+HLA-DR+ Treg cells which showed great similarities with classical CD4+ cells expressing forkhead box P3 (FOXP3). The shared features included the expression of programmed cell death protein 1 (PD-1), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), C-C chemokine receptor type 4 and 5 (CCR4 and CCR5), low expression of CD127, and a memory and effector-like phenotype. CD8+HLA-DR+ Treg-induced suppression on CD8+ responder T cells was abrogated by an anti-PD1 neutralizing antibody. Anti-PD-1 did not abrogate the suppressor effect induced on responder CD4+ T cells. In addition, CD8+HLA-DR+ Treg induced a preferential death on responder CD8+ T cells. This effect was not reversed by PD-1 neutralization. After activation, most CD8+HLA-DR+ Treg acquire programmed death-ligand 1 (PD-L1) expression. Interestingly, PD-L1 may induce apoptosis through CD80 expressed on activated CD8+ responder T cells. After PBMCs stimulation, CD8+HLA-DR+ Treg cells showed an increased frequency of IFN-γ and TNFα positive cells and higher degranulation. These data strongly argue against CD8+HLA-DR+ Treg being exhausted cells. Overall, the data presented in this study indicate that CD8+HLA-DR+ Treg and CD4+FOXP3+ Treg share phenotypic and functional features, which may provide cues to similar involvements in the control of antitumor immune responses and autoimmunity.https://www.frontiersin.org/article/10.3389/fimmu.2018.02788/fullCD8+HLA-DR+PD-1/PD-L1TIGITCCR4CD127regulatory T cells |
| spellingShingle | Andres Machicote Santiago Belén Placida Baz Luis A. Billordo Leonardo Fainboim Leonardo Fainboim Human CD8+HLA-DR+ Regulatory T Cells, Similarly to Classical CD4+Foxp3+ Cells, Suppress Immune Responses via PD-1/PD-L1 Axis Frontiers in Immunology CD8+HLA-DR+ PD-1/PD-L1 TIGIT CCR4 CD127 regulatory T cells |
| title | Human CD8+HLA-DR+ Regulatory T Cells, Similarly to Classical CD4+Foxp3+ Cells, Suppress Immune Responses via PD-1/PD-L1 Axis |
| title_full | Human CD8+HLA-DR+ Regulatory T Cells, Similarly to Classical CD4+Foxp3+ Cells, Suppress Immune Responses via PD-1/PD-L1 Axis |
| title_fullStr | Human CD8+HLA-DR+ Regulatory T Cells, Similarly to Classical CD4+Foxp3+ Cells, Suppress Immune Responses via PD-1/PD-L1 Axis |
| title_full_unstemmed | Human CD8+HLA-DR+ Regulatory T Cells, Similarly to Classical CD4+Foxp3+ Cells, Suppress Immune Responses via PD-1/PD-L1 Axis |
| title_short | Human CD8+HLA-DR+ Regulatory T Cells, Similarly to Classical CD4+Foxp3+ Cells, Suppress Immune Responses via PD-1/PD-L1 Axis |
| title_sort | human cd8 hla dr regulatory t cells similarly to classical cd4 foxp3 cells suppress immune responses via pd 1 pd l1 axis |
| topic | CD8+HLA-DR+ PD-1/PD-L1 TIGIT CCR4 CD127 regulatory T cells |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02788/full |
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