CD3-immunotoxin mediated depletion of T cells in lymphoid tissues of rhesus macaques
Lan Wang,
Gajendra W. Suryawanshi,
Shihyoung Kim,
Xin Guan,
Aylin C. Bonifacino,
Mark E. Metzger,
Robert E. Donahue,
Sanggu Kim,
Irvin S.Y. Chen
Affiliations
Lan Wang
Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, CA, 90095, USA; Division of Hematology-Oncology, Dept of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA
Gajendra W. Suryawanshi
Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, CA, 90095, USA; Division of Hematology-Oncology, Dept of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA
Shihyoung Kim
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, 43210, USA; Center for Retrovirus Research, The Ohio State University, Columbus, OH, 43210, USA; Infectious Disease Institute, The Ohio State University, Columbus, OH, 43210, USA
Xin Guan
Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, CA, 90095, USA; Division of Hematology-Oncology, Dept of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA
Aylin C. Bonifacino
Hematology Branch, National Heart, Lung and Blood Institute, NIH, Rockville, MD, 20850, USA
Mark E. Metzger
Hematology Branch, National Heart, Lung and Blood Institute, NIH, Rockville, MD, 20850, USA
Robert E. Donahue
Hematology Branch, National Heart, Lung and Blood Institute, NIH, Rockville, MD, 20850, USA
Sanggu Kim
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, 43210, USA; Center for Retrovirus Research, The Ohio State University, Columbus, OH, 43210, USA; Infectious Disease Institute, The Ohio State University, Columbus, OH, 43210, USA
Irvin S.Y. Chen
Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, CA, 90095, USA; Division of Hematology-Oncology, Dept of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA; UCLA AIDS Institute, UCLA, Los Angeles, CA, 90095, USA; Corresponding author. Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, 615 Charles E Young Drive South, Los Angeles, CA, 90024, USA.
Selective T-cell depletion prior to cell or organ transplantation is considered a preconditioning regimen to induce tolerance and immunosuppression. An immunotoxin consisting of a recombinant anti-CD3 antibody conjugated with diphtheria toxin was used to eliminate T-cells. It showed significant T-cell depletion activity in the peripheral blood and lymph nodes in animal models used in previous studies. To date, a comprehensive evaluation of T-cell depletion and CD3 proliferation for all lymphoid tissues has not been conducted. Here, two rhesus macaques were administered A-dmDT390-SCFBdb (CD3-IT) intravenously at 25 μg/kg twice daily for four days. Samples were collected one day prior to and four days post administration. Flow cytometry and immunofluorescence staining were used to evaluate treatment efficiency accurately. Our preliminary results suggest that CD3-IT treatment may induce higher depletion of CD3 and CD4 T-cells in the lymph nodes and spleen, but is ineffective in the colon and thymus. The data showed a better elimination tendency of CD4 T-cells in the B-cell zone relative to the germinal center in the lymph nodes. Further, CD3-IT treatment may lead to a reduction in germinal center T follicular helper CD4 cells in the lymph nodes compared to healthy controls. The number of proliferating CD3 T-cell indicated that repopulation in different lymphoid tissues may occur four days post treatment. Our results provide insights into the differential efficacy of CD3-IT treatment and T-cell proliferation post treatment in different lymphoid tissues. Overall, CD3-IT treatment shows potential efficacy in depleting T-cells in the periphery, lymph nodes, and spleen, making it a viable preconditioning regimen for cell or organ transplantation. Our pilot study provides critical descriptive statistics and can contribute to the design of larger future studies.
