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.
Max Planck Clinical Research Group, Department of Medicine III, University of Erlangen-Nuremberg, Germany.
G
G
Horneff
F
F
Emmrich
C
C
Reiter
J R
JR
Kalden
G R
GR
Burmester
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D015704:CD4 Antigens / Q000276:immunology*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002699:Chlorambucil / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015151:Immunoblotting; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D010641:Phenotype
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D002699:Chlorambucil