Long-term in vivo depletion of functional CD4(+) T lymphocytes from calvesrequires both thymectomy and anti-CD4 monoclonal antibody treatment

In vivo depletion of lymphocyte subsets is a direct approach used for disse ction of the mechanisms of protective immunity. Long-term in vivo depletion of bovine T lymphocyte subpopulations with monoclonal antibody (mAb) treat ment alone has been difficult to achieve. The objective of this study was t o determine whether both thymectomy and anti-CD4 mAb treatment would optimi ze long-term in vivo depletion of functional bovine CD4(+) T lymphocytes. C alves were thymectomized and treated with high doses of anti-CD4 mAb (appro ximately 5 mg/kg) over 4 days followed by subsequent lower doses (approxima tely 0.3 mg/kg) administered twice weekly for an additional 7 weeks. Deplet ion of CD4(+) T lymphocytes from blood, spleen and peripheral lymph nodes w as significantly improved in the thymectomized calves compared to thymus-in tact anti-CD4 mAb-treated calves. Significant differences in percentages of CD4(+) T lymphocytes between thymectomized and thymus-intact calves were s ustained for the duration of the 8-week study. Depletion of CD4(+) T lympho cytes from thymectomized calves resulted in complete abrogation of lymphopr oliferative responses to ovalbumin. In addition, thymectomized calves treat ed with anti-CD4 mAb had significantly reduced immunoglobulin G1 and no det ectable immunoglobulin G2 ovalbumin-specific antibody responses compared to thymus-intact anti-CD4 mAb-treated calves. The results of this study demon strate that both thymectomy and treatment with anti-CD4 mAb are required fo r long-term in vivo depletion of functional bovine CD4(+) T lymphocytes.