REPOPULATION OF BLOOD LYMPHOCYTE SUBPOPULATIONS IN RHEUMATOID-ARTHRITIS PATIENTS TREATED WITH THE DEPLETING HUMANIZED MONOCLONAL-ANTIBODY, CAMPATH-1H

Patients with severe rheumatoid arthritis who had failed treatment wit h conventional therapies were treated with a course of five or 10 dail y intravenous infusions of CAMPATH-1H, a humanized antibody against th e CD52 antigen, resulting in profound depletion of peripheral blood mo nonuclear cells. During the subsequent 18 months, lymphocytes were ana lysed for subpopulations by fluorescence-activated cell sorter (FAGS) and for proliferation in response to polyclonal T-cell stimulation wit h anti-CD3 or staphylococcal enterotoxin B (SEE). Treatment resulted i n almost complete depletion of lymphocytes from the blood followed by gradual repopulation. CD16(+) natural killer (NK) cells and CD14(+) mo nocytes returned to pretreatment levels within 1-2 months. CD19(+) B c ells returned to within 50% of pre-treatment levels by day 66 and to w ithin normal range by day 150, whereas CD8(+) T cells recovered to 50% of pretreatment levels by day 66, but did not show any further increa se during the rest of the study period. The most profound effects were on the CD4(+) T lymphocyte sub-population, as the mean CD4(+) count d id not increase above 20% of pre-treatment level at any time during th e study period (550 days), at all the doses tested. The T cells which initially repopulated the blood 1-2 months after treatment, nearly all expressed the activation markers human leucocyte antigen (HLA)-DR and CD45RO, although the percentage of T cells expressing these molecules gradually declined to normal levels over time. Proliferative response s to polyclonal T-cell stimulation (anti-CD3 and SEE) were also signif icantly reduced in the first few months after treatment, but recovered to pre-treatment levels by day 250. The relationship between these ob servations and the clinical response is discussed.