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Title: LONG-TERM IN VIVO DEPLETION OF FUNCTIONAL CD4+ LYMPHOCYTES FROM CALVES REQUIRES BOTH THYMECTOMY AND ANTI-CD4 MONOCLNAL ANTIBODY TREATMENT

Author
item Valdez, Reginald
item MCGUIRE, T - WASHINGTON STATE UNIV
item BROWN, W - WASHINGTON STATE UNIV
item DAVIS, W - WASHINGTON STATE UNIV
item Knowles Jr, Donald

Submitted to: Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/11/2001
Publication Date: N/A
Citation: N/A

Interpretive Summary: This manuscript provides methodology for achieving in vivo depletion of bovine CD4+ lymphocytes. This methodology allows for the dissection of the role of CD4+ lymphocytes in controlling infectious diseases such as Anaplasma marginale. The importance of this work is determining which components of the bovine immune response need to be stimulated via vaccination.

Technical Abstract: In vivo depletion of lymphocyte subsets is a direct approach used for dissection of the mechanisms of protective immunity. 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.