Long-term in vivo depletion of functional CD4+ T lymphocytes from calves requires both thymectomy and anti-CD4 monoclonal antibody treatment.
In vivo depletion of lymphocyte subsets is a direct approach used for dissection of the mechanisms of protective immunity. Long-term in vivo depletion of bovine T lymphocyte subpopulations with monoclonal antibody (mAb) treatment alone has been difficult to achieve. The objective of this study was to determine whether both thymectomy and anti-CD4 mAb treatment would optimize long-term in vivo depletion of functional bovine CD4+ T lymphocytes. Calves were thymectomized and treated with high doses of anti-CD4 mAb (approximately 5 mg/kg) over 4 days followed by subsequent lower doses (approximately 0.3 mg/kg) administered twice weekly for an additional 7 weeks. Depletion of CD4+ T lymphocytes from blood, spleen and peripheral lymph nodes was significantly improved in thymectomized calves compared to thymus-intact anti-CD4 mAb-treated calves. Significant differences in percentages of CD4+ T lymphocytes between thymectomized and thymus-intact calves were sustained for the duration of the 8-week study. Depletion of CD4+ T lymphocytes from thymectomized calves resulted in complete abrogation of lymphoproliferative responses to ovalbumin. In addition, thymectomized calves treated with anti-CD4 mAb had significantly reduced immunoglobulin G1 and no detectable immunoglobulin G2 ovalbumin-specific antibody responses compared to thymus-intact anti-CD4 mAb-treated calves. The results of this study demonstrate that both thymectomy and treatment with anti-CD4 mAb are required for long-term in vivo depletion of functional bovine CD4+ T lymphocytes.
Valdez
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RA
United States Department of Agriculture, Agricultural Research Service, Animal Disease Research Unit, Pullman, WA 99164-6630, USA. reg@vetmed.wsu.edu
McGuire
T C
TC
Brown
W C
WC
Davis
W C
WC
Knowles
D P
DP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002417:Cattle / Q000276:immunology*; D018929:Cell Culture Techniques; D002455:Cell Division / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007156:Immunologic Memory; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013934:Thymectomy; D013950:Thymus Gland / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D007074:Immunoglobulin G; D010047:Ovalbumin