Effects of anti‐CD4 antibody treatment on lymphocyte subsets and stimulated tumor necrosis factor alpha production

Abstract

T lymphocytes may play a central role in MS. The search for more targeted immunosuppression than is currently available has led to recent clinical trials of novel therapeutics. We studied 29 patients in a double-blind placebo-controlled trial of the chimeric monoclonal anti-CD4 antibody, cM-T412 (Centocor, Leiden, Holland) over a period of 18 months. Total and differential WBC counts; T, B, and natural killer lymphocytes; CD4+ and CD8+ T cells; CD4+ and CD4– naive cells; CD4+ and CD4– memory cells; interleukin-2 receptor- and major histocompatibility class II-positive T cells; serum tumor necrosis factor alpha (TNF-α); and PHA (phytohemagglutinin)/LPS (lipopolysaccharide)-stimulated whole blood TNF-α production were all examined serially in peripheral blood for the duration of the trial. In addition, for the first two treatment cycles, the above variables were tested 1 and 7 days after treatment. The results demonstrated significant long-term reductions, lasting up to 12 months after the last treatment cycle in all CD4+ subsets studied, but with a relative preservation of CD4+ memory cells as opposed to CD4+ naive cells. CD4– subsets also showed significant reductions after treatment but returned to baseline levels within 7 days. Monocyte counts were unaffected by cM-T412. Serum TNF-α and 2– and 18-hour PHN/LPS-stimulated TNF-α levels were also unchanged in the long term, although significant increases were observed in the 2– and 18-hour PHA/LPS-stimulated TNF-α levels the day immediately after treatment. There was no significant correlation between any of the immunologic markers studied and MRI measures of disease activity.