The human "Treg MLR" : immune monitoring for FOXP3+ T regulatory cell generation
BACKGROUND: Controversy exists about the conditions effecting the development of forkhead/winghead helix transcription factor P3 (FOXP3) expressing T cells and their relevance in transplant recipients.
METHODS: We generated carboxy-fluorescein diacetate succinimidyl ester-labeled CD4+CD25 high FOXP3+ cells in mixed lymphocyte reactions (MLRs) ("the Treg MLR"), with varying human leukocyte antigen (HLA) disparities and cell components. Five color flow cytometry and H-thymidine uptakes were the readouts.
RESULTS: (1) Despite lower stimulation indices (SIs) than two DR-mismatched MLRs, 2 DR-matched MLRs generated more than twofold higher percentages when gating on proliferating CD4+CD25 high FOXP3+ cells; (2) Even with low numbers of proliferating cells, autologous and HLA identical MLRs generated the highest FOXP3+:FOXP3- cell ratios; (3) Elimination of either non-CD3+ responding cells (resulting in "direct presentation" only) or responding CD25+ (Treg generating) cells increased the SI but inhibited proliferating CD4+CD25 high FOXP3+ cell development; (4) MLR-generated CD4+CD25 high FOXP3+ cells added as third components specifically inhibited the same freshly set MLR SI and caused recruitment of new CD4+CD25 high FOXP3+ cells. As an example of the "Treg MLR" immune monitoring potential, addition of third component peripheral blood mononuclear cell containing high percentages of CD4+CD25 high FOXP3+ cells from an HLA identical kidney transplant recipient (in a tolerance protocol) caused donor-specific Treg MLR inhibition or recruitment. This was similar to the third component MLR Tregs generated entirely in vitro.
CONCLUSION: In the Treg MLR, the generation of CD4+CD25 high FOXP3+ cells is more pronounced in the context of self-recognition (HLA matching, indirect presentation). These cells can be assayed for MLR inhibitory and Treg recruitment functions, so as to immunologically monitor the allospecific regulation after transplantation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2009 |
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| Erschienen: |
2009 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:88 |
|---|---|
| Enthalten in: |
Transplantation - 88(2009), 11 vom: 15. Dez., Seite 1303-11 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Levitsky, Josh [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 24.12.2009 Date Revised 20.10.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1097/TP.0b013e3181bbee98 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM193628627 |
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| 100 | 1 | |a Levitsky, Josh |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The human "Treg MLR" |b immune monitoring for FOXP3+ T regulatory cell generation |
| 264 | 1 | |c 2009 | |
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| 500 | |a Date Completed 24.12.2009 | ||
| 500 | |a Date Revised 20.10.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Controversy exists about the conditions effecting the development of forkhead/winghead helix transcription factor P3 (FOXP3) expressing T cells and their relevance in transplant recipients | ||
| 520 | |a METHODS: We generated carboxy-fluorescein diacetate succinimidyl ester-labeled CD4+CD25 high FOXP3+ cells in mixed lymphocyte reactions (MLRs) ("the Treg MLR"), with varying human leukocyte antigen (HLA) disparities and cell components. Five color flow cytometry and H-thymidine uptakes were the readouts | ||
| 520 | |a RESULTS: (1) Despite lower stimulation indices (SIs) than two DR-mismatched MLRs, 2 DR-matched MLRs generated more than twofold higher percentages when gating on proliferating CD4+CD25 high FOXP3+ cells; (2) Even with low numbers of proliferating cells, autologous and HLA identical MLRs generated the highest FOXP3+:FOXP3- cell ratios; (3) Elimination of either non-CD3+ responding cells (resulting in "direct presentation" only) or responding CD25+ (Treg generating) cells increased the SI but inhibited proliferating CD4+CD25 high FOXP3+ cell development; (4) MLR-generated CD4+CD25 high FOXP3+ cells added as third components specifically inhibited the same freshly set MLR SI and caused recruitment of new CD4+CD25 high FOXP3+ cells. As an example of the "Treg MLR" immune monitoring potential, addition of third component peripheral blood mononuclear cell containing high percentages of CD4+CD25 high FOXP3+ cells from an HLA identical kidney transplant recipient (in a tolerance protocol) caused donor-specific Treg MLR inhibition or recruitment. This was similar to the third component MLR Tregs generated entirely in vitro | ||
| 520 | |a CONCLUSION: In the Treg MLR, the generation of CD4+CD25 high FOXP3+ cells is more pronounced in the context of self-recognition (HLA matching, indirect presentation). These cells can be assayed for MLR inhibitory and Treg recruitment functions, so as to immunologically monitor the allospecific regulation after transplantation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
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| 650 | 7 | |a FOXP3 protein, human |2 NLM | |
| 650 | 7 | |a Forkhead Transcription Factors |2 NLM | |
| 650 | 7 | |a HLA Antigens |2 NLM | |
| 650 | 7 | |a IL2RA protein, human |2 NLM | |
| 650 | 7 | |a Interleukin-2 Receptor alpha Subunit |2 NLM | |
| 700 | 1 | |a Miller, Joshua |e verfasserin |4 aut | |
| 700 | 1 | |a Leventhal, Joseph |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Xuemei |e verfasserin |4 aut | |
| 700 | 1 | |a Flaa, Cathy |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Edward |e verfasserin |4 aut | |
| 700 | 1 | |a Tambur, Anat |e verfasserin |4 aut | |
| 700 | 1 | |a Burt, Richard K |e verfasserin |4 aut | |
| 700 | 1 | |a Gallon, Lorenzo |e verfasserin |4 aut | |
| 700 | 1 | |a Mathew, James M |e verfasserin |4 aut | |
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