EFFECTIVE IN-VIVO DEPLETION OF T-CELL SUBPOPULATIONS AND LOSS OF MEMORY CELLS IN CATTLE USING MOUSE MONOCLONAL-ANTIBODIES

Conditions were established to obtain depletion of T lymphocyte subset s in lymphoid tissues of calves by injection of mouse monoclonal antib odies to T cell antigens. Adverse reactions were avoided by injecting small quantities of antibody, until target cells had disappeared from blood. Two different mechanisms appeared to be responsible for elimina tion of the target cells. Rapid depletion of T cells was associated wi th complement-binding antibody isotypes (IgG2a, IgM), suggesting a com plement-mediated mechanism. Clearance of T cells after several days wa s observed with a non complement-binding isotype (IgG1), suggesting ph agocytosis or induction of apoptosis as possible mechanisms. Clearance of the cells in peripheral blood and spleen was obtained with 10-20 m g of anti-CD4 or anti-CD8, but almost ten times as much was needed to obtain depletion of the cells in lymph nodes and Peyer's patches. Depl etion lasted for 12 days for CD4 T cells and 3 weeks for CD8 T cells. Successful and lasting depletion (at least 2 weeks) was also obtained with other T cell reagents, such as anti-CD2 and anti-WC1 (gamma/delta T cells). Although B lymphocytes could be removed by a complement-bin ding antibody, complete depletion of these cells only lasted for a few hours, probably because B cells regenerate faster than T cells. T cel l function was severely inhibited when CD4(+) T cells were depleted. S timulation of T cells with foot and mouth disease viral antigen (FMDV) in vaccinated calves was non-existent after depletion. Even 2 months after restoration of normal CD4+ T cell levels in blood, activity to F MDV was low. This suggested that the depleted T cells were replaced by naive cells. (C) 1998 Published by Elsevier Science B.V. All rights r eserved.