Spatial regulation of CD8+ T cells at the HLA-E-NKG2A axis drives HIV persistence in lymph node B cell follicles
Summary: B cell follicles (BCFs) in the lymph node are a major sanctuary for HIV reservoirs. Immune regulatory mechanisms hindering cytolytic CD8+ responses at these sites are poorly characterized, likely enabling HIV persistence. Spatial transcriptomics and high-dimensional histocytometry were used...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-09-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725009520 |
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| author | Andrea O. Papadopoulos Leonard Mvaya Trevor Khaba Namani Ngema Werner Smidt Sibongiseni Msipa Bongiwe Mahlobo Thandekile Ngubane Krista Dong Ismail Jajbhay Johan Pansegrouw Kondwani Jambo Zaza Ndhlovu |
| author_facet | Andrea O. Papadopoulos Leonard Mvaya Trevor Khaba Namani Ngema Werner Smidt Sibongiseni Msipa Bongiwe Mahlobo Thandekile Ngubane Krista Dong Ismail Jajbhay Johan Pansegrouw Kondwani Jambo Zaza Ndhlovu |
| author_sort | Andrea O. Papadopoulos |
| collection | DOAJ |
| description | Summary: B cell follicles (BCFs) in the lymph node are a major sanctuary for HIV reservoirs. Immune regulatory mechanisms hindering cytolytic CD8+ responses at these sites are poorly characterized, likely enabling HIV persistence. Spatial transcriptomics and high-dimensional histocytometry were used to define CD8+ T cell function and immune regulation in lymph node (LN) follicles of people living with HIV (PLWH), at various stages of antiretroviral therapy (ART) treatment. Histocytometry demonstrated that CD8+ T cells infiltrating BCFs mostly lacked granzyme B expression, coinciding with reduced chromatin access at cytolytic gene loci in dissociated lymph node cells. Spatial transcriptomics confirmed the immune regulatory microenvironment of HIV-infected BCFs, particularly exhibiting upregulation of HLA-E. Additional fluorescence-activated cell sorting (FACS) analysis identified a subset of LN CD8+ T cells expressing the NKG2A-interacting partner of HLA-E, with reduced granzyme B expression. These findings suggest that regulation of follicular CD8+ T cells at the HLA-E-NKG2A axis may be a key mechanism for HIV immune evasion. |
| format | Article |
| id | doaj-art-731cc46053c8434287be45958bfcf564 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-731cc46053c8434287be45958bfcf5642025-08-24T05:12:08ZengElsevierCell Reports2211-12472025-09-0144911618110.1016/j.celrep.2025.116181Spatial regulation of CD8+ T cells at the HLA-E-NKG2A axis drives HIV persistence in lymph node B cell folliclesAndrea O. Papadopoulos0Leonard Mvaya1Trevor Khaba2Namani Ngema3Werner Smidt4Sibongiseni Msipa5Bongiwe Mahlobo6Thandekile Ngubane7Krista Dong8Ismail Jajbhay9Johan Pansegrouw10Kondwani Jambo11Zaza Ndhlovu12Africa Health Research Institute, Durban, South AfricaMalawi-Liverpool-Wellcome Research Programme, Blantyre, MalawiHIV Pathogenesis Programme, UKZN, Durban, South AfricaAfrica Health Research Institute, Durban, South AfricaAfrica Health Research Institute, Durban, South AfricaAfrica Health Research Institute, Durban, South AfricaAfrica Health Research Institute, Durban, South AfricaHIV Pathogenesis Programme, UKZN, Durban, South AfricaRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USAPrince Mshiyeni Hospital, Durban, South AfricaPrince Mshiyeni Hospital, Durban, South AfricaMalawi-Liverpool-Wellcome Research Programme, Blantyre, Malawi; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UKAfrica Health Research Institute, Durban, South Africa; HIV Pathogenesis Programme, UKZN, Durban, South Africa; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Corresponding authorSummary: B cell follicles (BCFs) in the lymph node are a major sanctuary for HIV reservoirs. Immune regulatory mechanisms hindering cytolytic CD8+ responses at these sites are poorly characterized, likely enabling HIV persistence. Spatial transcriptomics and high-dimensional histocytometry were used to define CD8+ T cell function and immune regulation in lymph node (LN) follicles of people living with HIV (PLWH), at various stages of antiretroviral therapy (ART) treatment. Histocytometry demonstrated that CD8+ T cells infiltrating BCFs mostly lacked granzyme B expression, coinciding with reduced chromatin access at cytolytic gene loci in dissociated lymph node cells. Spatial transcriptomics confirmed the immune regulatory microenvironment of HIV-infected BCFs, particularly exhibiting upregulation of HLA-E. Additional fluorescence-activated cell sorting (FACS) analysis identified a subset of LN CD8+ T cells expressing the NKG2A-interacting partner of HLA-E, with reduced granzyme B expression. These findings suggest that regulation of follicular CD8+ T cells at the HLA-E-NKG2A axis may be a key mechanism for HIV immune evasion.http://www.sciencedirect.com/science/article/pii/S2211124725009520CP: Immunology |
| spellingShingle | Andrea O. Papadopoulos Leonard Mvaya Trevor Khaba Namani Ngema Werner Smidt Sibongiseni Msipa Bongiwe Mahlobo Thandekile Ngubane Krista Dong Ismail Jajbhay Johan Pansegrouw Kondwani Jambo Zaza Ndhlovu Spatial regulation of CD8+ T cells at the HLA-E-NKG2A axis drives HIV persistence in lymph node B cell follicles Cell Reports CP: Immunology |
| title | Spatial regulation of CD8+ T cells at the HLA-E-NKG2A axis drives HIV persistence in lymph node B cell follicles |
| title_full | Spatial regulation of CD8+ T cells at the HLA-E-NKG2A axis drives HIV persistence in lymph node B cell follicles |
| title_fullStr | Spatial regulation of CD8+ T cells at the HLA-E-NKG2A axis drives HIV persistence in lymph node B cell follicles |
| title_full_unstemmed | Spatial regulation of CD8+ T cells at the HLA-E-NKG2A axis drives HIV persistence in lymph node B cell follicles |
| title_short | Spatial regulation of CD8+ T cells at the HLA-E-NKG2A axis drives HIV persistence in lymph node B cell follicles |
| title_sort | spatial regulation of cd8 t cells at the hla e nkg2a axis drives hiv persistence in lymph node b cell follicles |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725009520 |
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