Persistent depletion of CD4+ T cells and inversion of the CD4/CD8 T cell ratio induced by anti-CD4 therapy.

A 49-year-old patient with refractory rheumatoid arthritis was treated repeatedly with anti-CD4 murine monoclonal antibodies. While the first anti-CD4 treatment resulted in a marked, however transient, depletion of CD4+ cells from 1070 to a minimum of 175/microliters, a second treatment cycle resulted in a persistent decrease. Despite this marked depletion, no major clinical improvement occurred, which was in striking contrast to other patients treated in a similar way. Of interest, the administration of low doses of chlorambucil led to significant clinical benefits. Markedly reduced numbers of CD4+ cells (200-500/microliters) were observed for more than 2 years, while the numbers of CD8+ cells increased after the second treatment. No infectious episodes occurred. Discontinuation of chlorambucil did not lead to increasing amounts of CD4+ cells. In contrast to the rapid reduction of CD4+ cells from the blood stream induced by anti-CD4 infusions, there was a considerable delay until altered CD4/CD8 ratios were observed in intraarticular sites. No evidence was found for either humoral or cellular immune reactivities towards CD4+ T helper cells. Our findings suggest that in certain patients undergoing anti-CD4 therapy there may be a reduced capacity of the CD4+ T helper cell pool to regenerate.