TY - JOUR
T1 - 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
AU - Herman, Shoshy
AU - Zurgil, Naomi
AU - Langevitz, Pnina
AU - Ehrenfeld, Michael
AU - Deutsch, Mordechai
N1 - Funding Information:
We assume from these findings that MTX effects immunosuppression only in the active RA patients, who exhibit a major blast lymphocyte population. This assumption is supported by our previous results (Herman et al., 2003), which demonstrate (by widely accepted techniques of apoptosis detection) that MTX apoptotic effect is found only in activated healthy mononuclear cells, i.e., blast lymphocytes, but not in resting lymphocytes. This phenomenon has been reported by Genestier et al. (1998) and Fairbanks et al. (1999). The assumption is also supported by the presently reported results of FDA hyperpolarization. The monitored changes in fluorescence polarization reflect the intracellular plasma viscosity, during either lymphocyte stimulation (Deutsch et al., 2000; Kaplan et al., 1997) or early apoptotic signal (Zurgil et al., 2000), thus providing a valuable indicator of cellular functionality (Cercek et al., 1974; Shapiro, 1995; Yishai et al., 2003).
Funding Information:
supported by the Horowitz Foundation.
PY - 2004
Y1 - 2004
N2 - 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.
AB - 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.
KW - CD4+ T lymphocytes
KW - Individual cell scanner (ICS)
KW - Methotrexate (MTX)
KW - Rheumatoid arthritis (RA)
UR - http://www.scopus.com/inward/record.url?scp=4644282236&partnerID=8YFLogxK
U2 - 10.1081/IMM-120039865
DO - 10.1081/IMM-120039865
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AN - SCOPUS:4644282236
SN - 0882-0139
VL - 33
SP - 351
EP - 362
JO - Immunological Investigations
JF - Immunological Investigations
IS - 3
ER -