Antibody-mediated depletion of select leukocyte subsets in blood and tissue of nonhuman primates
Understanding the immunological control of pathogens requires a detailed evaluation of the mechanistic contributions of individual cell types within the immune system. While knockout mouse models that lack certain cell types have been used to help define the role of those cells, the biological and p...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1359679/full |
| _version_ | 1797266439191658496 |
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| author | Matthew S. Sutton Allison N. Bucsan Chelsea C. Lehman Megha Kamath Supriya Pokkali Diogo M. Magnani Robert Seder Patricia A. Darrah Mario Roederer |
| author_facet | Matthew S. Sutton Allison N. Bucsan Chelsea C. Lehman Megha Kamath Supriya Pokkali Diogo M. Magnani Robert Seder Patricia A. Darrah Mario Roederer |
| author_sort | Matthew S. Sutton |
| collection | DOAJ |
| description | Understanding the immunological control of pathogens requires a detailed evaluation of the mechanistic contributions of individual cell types within the immune system. While knockout mouse models that lack certain cell types have been used to help define the role of those cells, the biological and physiological characteristics of mice do not necessarily recapitulate that of a human. To overcome some of these differences, studies often look towards nonhuman primates (NHPs) due to their close phylogenetic relationship to humans. To evaluate the immunological role of select cell types, the NHP model provides distinct advantages since NHP more closely mirror the disease manifestations and immunological characteristics of humans. However, many of the experimental manipulations routinely used in mice (e.g., gene knock-out) cannot be used with the NHP model. As an alternative, the in vivo infusion of monoclonal antibodies that target surface proteins on specific cells to either functionally inhibit or deplete cells can be a useful tool. Such depleting antibodies have been used in NHP studies to address immunological mechanisms of action. In these studies, the extent of depletion has generally been reported for blood, but not thoroughly assessed in tissues. Here, we evaluated four depleting regimens that primarily target T cells in NHP: anti-CD4, anti-CD8α, anti-CD8β, and immunotoxin-conjugated anti-CD3. We evaluated these treatments in healthy unvaccinated and IV BCG-vaccinated NHP to measure the extent that vaccine-elicited T cells – which may be activated, increased in number, or resident in specific tissues – are depleted compared to resting populations in unvaccinated NHPs. We report quantitative measurements of in vivo depletion at multiple tissue sites providing insight into the range of cell types depleted by a given mAb. While we found substantial depletion of target cell types in blood and tissue of many animals, residual cells remained, often residing within tissue. Notably, we find that animal-to-animal variation is substantial and consequently studies that use these reagents should be powered accordingly. |
| first_indexed | 2024-04-25T01:00:42Z |
| format | Article |
| id | doaj.art-95faee24c36f4d139c41cce54445ee40 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-25T01:00:42Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-95faee24c36f4d139c41cce54445ee402024-03-11T04:40:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13596791359679Antibody-mediated depletion of select leukocyte subsets in blood and tissue of nonhuman primatesMatthew S. Sutton0Allison N. Bucsan1Chelsea C. Lehman2Megha Kamath3Supriya Pokkali4Diogo M. Magnani5Robert Seder6Patricia A. Darrah7Mario Roederer8Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United StatesNonhuman Primate Reagent Resource, University of Massachusetts Chan Medical School, Worcester, MA, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United StatesUnderstanding the immunological control of pathogens requires a detailed evaluation of the mechanistic contributions of individual cell types within the immune system. While knockout mouse models that lack certain cell types have been used to help define the role of those cells, the biological and physiological characteristics of mice do not necessarily recapitulate that of a human. To overcome some of these differences, studies often look towards nonhuman primates (NHPs) due to their close phylogenetic relationship to humans. To evaluate the immunological role of select cell types, the NHP model provides distinct advantages since NHP more closely mirror the disease manifestations and immunological characteristics of humans. However, many of the experimental manipulations routinely used in mice (e.g., gene knock-out) cannot be used with the NHP model. As an alternative, the in vivo infusion of monoclonal antibodies that target surface proteins on specific cells to either functionally inhibit or deplete cells can be a useful tool. Such depleting antibodies have been used in NHP studies to address immunological mechanisms of action. In these studies, the extent of depletion has generally been reported for blood, but not thoroughly assessed in tissues. Here, we evaluated four depleting regimens that primarily target T cells in NHP: anti-CD4, anti-CD8α, anti-CD8β, and immunotoxin-conjugated anti-CD3. We evaluated these treatments in healthy unvaccinated and IV BCG-vaccinated NHP to measure the extent that vaccine-elicited T cells – which may be activated, increased in number, or resident in specific tissues – are depleted compared to resting populations in unvaccinated NHPs. We report quantitative measurements of in vivo depletion at multiple tissue sites providing insight into the range of cell types depleted by a given mAb. While we found substantial depletion of target cell types in blood and tissue of many animals, residual cells remained, often residing within tissue. Notably, we find that animal-to-animal variation is substantial and consequently studies that use these reagents should be powered accordingly.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1359679/fullin vivo depletionnonhuman primatesMT807R1CD4R1CD8β255R1C207 |
| spellingShingle | Matthew S. Sutton Allison N. Bucsan Chelsea C. Lehman Megha Kamath Supriya Pokkali Diogo M. Magnani Robert Seder Patricia A. Darrah Mario Roederer Antibody-mediated depletion of select leukocyte subsets in blood and tissue of nonhuman primates Frontiers in Immunology in vivo depletion nonhuman primates MT807R1 CD4R1 CD8β255R1 C207 |
| title | Antibody-mediated depletion of select leukocyte subsets in blood and tissue of nonhuman primates |
| title_full | Antibody-mediated depletion of select leukocyte subsets in blood and tissue of nonhuman primates |
| title_fullStr | Antibody-mediated depletion of select leukocyte subsets in blood and tissue of nonhuman primates |
| title_full_unstemmed | Antibody-mediated depletion of select leukocyte subsets in blood and tissue of nonhuman primates |
| title_short | Antibody-mediated depletion of select leukocyte subsets in blood and tissue of nonhuman primates |
| title_sort | antibody mediated depletion of select leukocyte subsets in blood and tissue of nonhuman primates |
| topic | in vivo depletion nonhuman primates MT807R1 CD4R1 CD8β255R1 C207 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1359679/full |
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