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

Shoshy Herman; Naomi Zurgil; Pnina Langevitz; Michael Ehrenfeld; Mordechai Deutsch

doi:10.1081/imm-120039865

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

Shoshy Herman
, Naomi Zurgil
, Pnina Langevitz
, Michael Ehrenfeld
, Mordechai Deutsch

Department of Physics - at Bar-Ilan University

Bar-Ilan University
Sheba Medical Center at Tel Hashomer

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	351-362
Number of pages	12
Journal	Immunological Investigations
Volume	33
Issue number	3
DOIs	https://doi.org/10.1081/imm-120039865
State	Published - 2004

Bibliographical note

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.

Funding

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). supported by the Horowitz Foundation.

Funders
Food and Drug Administration
Horowitz Foundation for Social Policy

Keywords

CD4+ T lymphocytes
Individual cell scanner (ICS)
Methotrexate (MTX)
Rheumatoid arthritis (RA)

Access to Document

10.1081/imm-120039865

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this

@article{2af75d8659214b06aba1d546fd0b7c86,

title = "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",

abstract = "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.",

keywords = "CD4+ T lymphocytes, Individual cell scanner (ICS), Methotrexate (MTX), Rheumatoid arthritis (RA)",

author = "Shoshy Herman and Naomi Zurgil and Pnina Langevitz and Michael Ehrenfeld and Mordechai Deutsch",

note = "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.",

year = "2004",

doi = "10.1081/imm-120039865",

language = "אנגלית",

volume = "33",

pages = "351--362",

journal = "Immunological Investigations",

issn = "0882-0139",

publisher = "Taylor \& Francis Group LLC Philadelphia",

number = "3",

}

Herman, S, Zurgil, N, Langevitz, P, Ehrenfeld, M & Deutsch, M 2004, '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', Immunological Investigations, vol. 33, no. 3, pp. 351-362. https://doi.org/10.1081/imm-120039865

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. / Herman, Shoshy; Zurgil, Naomi; Langevitz, Pnina et al.
In: Immunological Investigations, Vol. 33, No. 3, 2004, p. 351-362.

Research output: Contribution to journal › Article › peer-review

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 - https://www.scopus.com/pages/publications/4644282236

U2 - 10.1081/imm-120039865

DO - 10.1081/imm-120039865

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

SN - 0882-0139

VL - 33

SP - 351

EP - 362

JO - Immunological Investigations

JF - Immunological Investigations

IS - 3

ER -

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

Abstract

Bibliographical note

Funding

Keywords

Access to Document

Other files and links

Fingerprint

Cite this