The immunosuppressive effect of methotrexate in active rheumatoid arthritis patients vs. its stimulatory effect in nonactive patients, as indicated by cytometric measurements of CD4+ T cell subpopulations.
This cytometric study assesses the effects of methotrexate (MTX) on the expanded CD4+ lymphocyte population in active and nonactive rheumatoid arthritis (RA) patients. In the active patients, MTX was found to reduce the predominant CD4+ CD28+ subpopulation (by 30%), and the minor subpopulation of CD4+ CD28- (by 34%). The incidence of CD25 phenotype was downregulated by 15%. These reductions can be attributed to immunosuppression through apoptosis, which was demonstrated by MTX-induced fluorescein diacetate (FDA) hyperpolarization (an established indicator of early apoptosis). In contrast, in nonactive RA patients, the major CD4+ CD28+ subpopulation of small lymphocytes appeared to be activated by MTX, subsequently transforming into a major hyperblast population, whereas the minor CD4+ CD28- subpopulation was not affected by MTX treatment. The activation by MTX in this group of patients is evidenced by MTX-induced FDA depolarization (an indicator of early activation). Thus, MTX immunosuppressive effect on CD4+ subsets was found in active patients, whereas immunostimulation by MTX was shown in nonactive patients. The found discriminative effect of MTX may suggest a higher effectiveness of low-dose MTX therapy in active RA patients.
Herman
Shoshy
S
Physics Department, The Biophysical Interdisciplinary Jerome Schottenstein Center for the Research and the Technology of the Cellome, Bar-Ilan University, Ramat-Gan, Israel.
Zurgil
Naomi
N
Langevitz
Pnina
P
Ehrenfeld
Michael
M
Deutsch
Mordechai
M
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D005434:Flow Cytometry; D005454:Fluorescence Polarization; D006801:Humans; D007165:Immunosuppression Therapy; D008727:Methotrexate / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged
D018501:Antirheumatic Agents; D018106:CD28 Antigens; D008727:Methotrexate