Treatment with depleting CD4 monoclonal antibody results in a preferential loss of circul;ating naive T cells but does not affect IFN-gamma secreting TH1 cells in humans

M.H.G. Rep, B.W. van Oosten, M.T.L. Roos, H.J. Adèr, C.H. Polman, R.A.W. van Lier

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CD4(pos) TH1 T cells are considered to play a central role in a number of human autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis. Experimental treatment protocols aimed at selectively eliminating CD4(pos) T cells thus far have yielded disappointing clinical results. Here we analyzed phenotype and function of circulating T cells in multiple sclerosis patients treated with the chimeric CD4 mAb cM-T412 in a randomized, double-blind, placebo-controlled, magnetic resonance imaging-monitored phase II trial. Treatment resulted in a long-lasting depletion of CD4(pos) T cells but did not affect CD8(pos) T cell numbers. Analysis of CD4(pos) subpopulations showed that unprimed, CD45RA(pos)/R0(neg) lymphocytes were approximately three times more sensitive to the mAb than primed, CD45RA(neg)/R0(pos) T cells. Notably, within the CD45RA(pos) subset, T cells with phenotypic evidence of prior activation, i.e., expressing Fas, were relatively insensitive to cM-T412, compared with Fas(neg) cells. Remarkably, while a decrease in the number of IL-4-producing T helper 2 (TH2)-type cells in the anti-CD4 treated group was observed, numbers of IFN-gamma-producing T helper 1 (TH1)-type cells remained stable, resulting in a significant increase in the TH1/TH2 ratio. Our data show that treatment with depleting CD4 mAb does not eliminate the cells most strongly involved in the disease process, i.e., primed, IFN-gamma-producing TH1-type cells, and may therefore give an explanation for the lack of beneficial clinical effects of depleting CD4 mAb in human chronic autoimmune disease
Original languageUndefined/Unknown
Pages (from-to)2225-2231
Number of pages7
JournalThe journal of clinical investigation
Issue number9
Publication statusPublished - 1 May 1997


  • AMC wi-eigen
  • CD4 antibodies, monoclonal
  • T lymphocyte subsets
  • Thl cells
  • autoimmune diseases therapy
  • multiple sclerosis

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