Changes in Frequency and Activation Status of Major CD4+ T-Cell Subsets after Initiation of Immunosuppressive Therapy in a Patient with New Diagnosis Childhood-Onset Systemic Lupus Erythematosus
BackgroundSeveral studies suggest that defects of regulatory T-cells (Tregs) and impaired cellular immunity are secondary to an imbalance between auto-aggressive T-cells and Tregs in lupus patients. Discrepancies in Tregs and effector T-cells (Teff) in active lupus patients are shown to be restored...
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Frontiers Media S.A.
2017-05-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fped.2017.00104/full |
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| author | Saimun Singla Saimun Singla Scott E. Wenderfer Scott E. Wenderfer Eyal Muscal Eyal Muscal Anna Carmela P. Sagcal-Gironella Anna Carmela P. Sagcal-Gironella Jordan S. Orange Jordan S. Orange George Makedonas George Makedonas |
| author_facet | Saimun Singla Saimun Singla Scott E. Wenderfer Scott E. Wenderfer Eyal Muscal Eyal Muscal Anna Carmela P. Sagcal-Gironella Anna Carmela P. Sagcal-Gironella Jordan S. Orange Jordan S. Orange George Makedonas George Makedonas |
| author_sort | Saimun Singla |
| collection | DOAJ |
| description | BackgroundSeveral studies suggest that defects of regulatory T-cells (Tregs) and impaired cellular immunity are secondary to an imbalance between auto-aggressive T-cells and Tregs in lupus patients. Discrepancies in Tregs and effector T-cells (Teff) in active lupus patients are shown to be restored in patients upon receiving immunosuppressive therapy. Therefore, our main aim was to observe frequencies of these CD4+ T-cell subsets and Tregs/Teff ratio in a new diagnosis of childhood-onset systemic lupus erythematous (cSLE) before and after initiation of therapy. In addition, we monitored T-cell exhaustion status by examining responses to super-antigen staphylococcal enterotoxin B (SEB) and PD-1 expression in this patient.MethodsPhenotyping of CD4+ T-cell subsets was carried out under basal conditions and after SEB stimulation using flow cytometry in one inactive (I-cSLE) and one active cSLE (A-cSLE) patient, as well as a healthy control (HC). The A-cSLE patient was a new diagnosis. Variables were measured at three consecutive time points in the active patient, reflecting various stages of disease activity. Activation status of CD4+ T-cells in the A-cSLE patient was compared to that of the I-cSLE patient and HC. Disease activity was measured by calculating the systemic lupus erythematous disease activity index.ResultsWe found that the A-cSLE patient was not Tregs deficient. The patient had increased frequency of Tregs, and the Tregs/Teff ratio increased when the disease activity became less severe. CD4+ T-cells in the I-cSLE patient and in the A-cSLE patient with milder disease activity had heightened responsiveness to SEB, whereas T-cells were relatively hypo-responsive to SEB in the A-cSLE patient when disease activity was higher. The active patient exhibited higher frequencies of PD-1+ expressing Tregs, Teff, and Tnaïve/mem cells under basal conditions compared to the HC and I-cSLE patient.ConclusionIn the A-cSLE patient, changes in Tregs/Teff ratio correlated better with clinical improvement compared to Tregs frequencies alone and might reflect the restoration of immune homeostasis with therapy. SEB hypo-responsiveness in the A-cSLE patient when disease activity was higher paralleled with findings of greater frequencies of PD-1+ expressing Tregs, Teff, and Tnaïve/mem cells, suggests a possible global exhaustion status of CD4+ T-cells in this patient. |
| first_indexed | 2024-12-21T01:47:49Z |
| format | Article |
| id | doaj.art-ea729a38e80a4a6ea9c74aa215394f3f |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-12-21T01:47:49Z |
| publishDate | 2017-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pediatrics |
| spelling | doaj.art-ea729a38e80a4a6ea9c74aa215394f3f2022-12-21T19:19:58ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602017-05-01510.3389/fped.2017.00104238578Changes in Frequency and Activation Status of Major CD4+ T-Cell Subsets after Initiation of Immunosuppressive Therapy in a Patient with New Diagnosis Childhood-Onset Systemic Lupus ErythematosusSaimun Singla0Saimun Singla1Scott E. Wenderfer2Scott E. Wenderfer3Eyal Muscal4Eyal Muscal5Anna Carmela P. Sagcal-Gironella6Anna Carmela P. Sagcal-Gironella7Jordan S. Orange8Jordan S. Orange9George Makedonas10George Makedonas11Department of Pediatrics, Baylor College of Medicine, Houston, TX, USADivision of Allergy, Immunology and Rheumatology, Texas Children’s Hospital, Houston, TX, USADepartment of Pediatrics, Baylor College of Medicine, Houston, TX, USARenal Section, Texas Children’s Hospital, Houston, TX, USADepartment of Pediatrics, Baylor College of Medicine, Houston, TX, USADivision of Allergy, Immunology and Rheumatology, Texas Children’s Hospital, Houston, TX, USADepartment of Pediatrics, Baylor College of Medicine, Houston, TX, USADivision of Allergy, Immunology and Rheumatology, Texas Children’s Hospital, Houston, TX, USADepartment of Pediatrics, Baylor College of Medicine, Houston, TX, USADivision of Allergy, Immunology and Rheumatology, Texas Children’s Hospital, Houston, TX, USADepartment of Pediatrics, Baylor College of Medicine, Houston, TX, USADivision of Allergy, Immunology and Rheumatology, Texas Children’s Hospital, Houston, TX, USABackgroundSeveral studies suggest that defects of regulatory T-cells (Tregs) and impaired cellular immunity are secondary to an imbalance between auto-aggressive T-cells and Tregs in lupus patients. Discrepancies in Tregs and effector T-cells (Teff) in active lupus patients are shown to be restored in patients upon receiving immunosuppressive therapy. Therefore, our main aim was to observe frequencies of these CD4+ T-cell subsets and Tregs/Teff ratio in a new diagnosis of childhood-onset systemic lupus erythematous (cSLE) before and after initiation of therapy. In addition, we monitored T-cell exhaustion status by examining responses to super-antigen staphylococcal enterotoxin B (SEB) and PD-1 expression in this patient.MethodsPhenotyping of CD4+ T-cell subsets was carried out under basal conditions and after SEB stimulation using flow cytometry in one inactive (I-cSLE) and one active cSLE (A-cSLE) patient, as well as a healthy control (HC). The A-cSLE patient was a new diagnosis. Variables were measured at three consecutive time points in the active patient, reflecting various stages of disease activity. Activation status of CD4+ T-cells in the A-cSLE patient was compared to that of the I-cSLE patient and HC. Disease activity was measured by calculating the systemic lupus erythematous disease activity index.ResultsWe found that the A-cSLE patient was not Tregs deficient. The patient had increased frequency of Tregs, and the Tregs/Teff ratio increased when the disease activity became less severe. CD4+ T-cells in the I-cSLE patient and in the A-cSLE patient with milder disease activity had heightened responsiveness to SEB, whereas T-cells were relatively hypo-responsive to SEB in the A-cSLE patient when disease activity was higher. The active patient exhibited higher frequencies of PD-1+ expressing Tregs, Teff, and Tnaïve/mem cells under basal conditions compared to the HC and I-cSLE patient.ConclusionIn the A-cSLE patient, changes in Tregs/Teff ratio correlated better with clinical improvement compared to Tregs frequencies alone and might reflect the restoration of immune homeostasis with therapy. SEB hypo-responsiveness in the A-cSLE patient when disease activity was higher paralleled with findings of greater frequencies of PD-1+ expressing Tregs, Teff, and Tnaïve/mem cells, suggests a possible global exhaustion status of CD4+ T-cells in this patient.http://journal.frontiersin.org/article/10.3389/fped.2017.00104/fullT regulatory cellsT effector cellschildhood-onset systemic lupus erythematosusT-cell exhaustionPD-1 |
| spellingShingle | Saimun Singla Saimun Singla Scott E. Wenderfer Scott E. Wenderfer Eyal Muscal Eyal Muscal Anna Carmela P. Sagcal-Gironella Anna Carmela P. Sagcal-Gironella Jordan S. Orange Jordan S. Orange George Makedonas George Makedonas Changes in Frequency and Activation Status of Major CD4+ T-Cell Subsets after Initiation of Immunosuppressive Therapy in a Patient with New Diagnosis Childhood-Onset Systemic Lupus Erythematosus Frontiers in Pediatrics T regulatory cells T effector cells childhood-onset systemic lupus erythematosus T-cell exhaustion PD-1 |
| title | Changes in Frequency and Activation Status of Major CD4+ T-Cell Subsets after Initiation of Immunosuppressive Therapy in a Patient with New Diagnosis Childhood-Onset Systemic Lupus Erythematosus |
| title_full | Changes in Frequency and Activation Status of Major CD4+ T-Cell Subsets after Initiation of Immunosuppressive Therapy in a Patient with New Diagnosis Childhood-Onset Systemic Lupus Erythematosus |
| title_fullStr | Changes in Frequency and Activation Status of Major CD4+ T-Cell Subsets after Initiation of Immunosuppressive Therapy in a Patient with New Diagnosis Childhood-Onset Systemic Lupus Erythematosus |
| title_full_unstemmed | Changes in Frequency and Activation Status of Major CD4+ T-Cell Subsets after Initiation of Immunosuppressive Therapy in a Patient with New Diagnosis Childhood-Onset Systemic Lupus Erythematosus |
| title_short | Changes in Frequency and Activation Status of Major CD4+ T-Cell Subsets after Initiation of Immunosuppressive Therapy in a Patient with New Diagnosis Childhood-Onset Systemic Lupus Erythematosus |
| title_sort | changes in frequency and activation status of major cd4 t cell subsets after initiation of immunosuppressive therapy in a patient with new diagnosis childhood onset systemic lupus erythematosus |
| topic | T regulatory cells T effector cells childhood-onset systemic lupus erythematosus T-cell exhaustion PD-1 |
| url | http://journal.frontiersin.org/article/10.3389/fped.2017.00104/full |
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