Inhibition of antigen-specific activation of an L3T4+ T cell line by cyclosporine with maintenance of macrophage-mediated antigen presentation

C. Y. Lu, P. A. Lemay, M. J. Lombardi

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Cyclosporine has clearly been shown to directly inhibit T lymphocyte activation by monoclonal antibodies or mitogens where nominal antigen and accessory cells are not present. However, when T lymphocytes are stimulated by antigen, as occurs in allograft rejection, T lymphocytes and accessory cells must interact with one another. Under the latter circumstances, the issue of whether cyclosporine acts on T lymphocyte, accessory cell, or both is not resolved. This issue is addressed in this study. To assess the effect of cyclosporine on T cell activation, macrophages were incubated with heat-killed Listeria and then fixed in paraformaldehyde. These fixed macrophages retained their ability to present antigen to T cells but were not affected by subsequent treatment with cyclosporine. When cyclosporine and a L3T4+ T lymphocyte line were added simultaneously to fixed, antigen-pulsed macrophages, the drug inhibited antigen-specific T cell activation with a half maximal inhibitory concentration of 10 ng/ml. To our knowledge, this is the first evidence that low doses of cyclosporine inhibit antigen-specific T cell activation where the drug's effects on antigen-presenting cells have been excluded. To assess the effects of cyclosporine on macrophage-mediated antigen-presentation, macrophages were exposed simultaneously to cyclosporine and antigen, and then fixed. Antigen-presentation was not inhibited unless extremely large doses (9000 ng/ml) of cyclosporine were used. In our experimental system, any new inhibitory activity acquired by live cyclosporine-treated macrophages could be explained by residual drug. Finally, cyclosporine did not inhibit the induction of macrophage Ia expression nor antigen-presenting function after stimulation in vitro with lymphokine.

Original languageEnglish (US)
Pages (from-to)187-194
Number of pages8
JournalTransplantation
Volume45
Issue number1
StatePublished - 1988

Fingerprint

Antigen Presentation
Cyclosporine
Macrophages
Maintenance
T-Lymphocytes
Antigens
Cell Line
CD27 Antigens
Pharmaceutical Preparations
Listeria
Macrophage Activation
Lymphokines
Antigen-Presenting Cells
Lymphocyte Activation
Mitogens
Allografts
Hot Temperature
Monoclonal Antibodies

ASJC Scopus subject areas

  • Immunology
  • Transplantation

Cite this

Inhibition of antigen-specific activation of an L3T4+ T cell line by cyclosporine with maintenance of macrophage-mediated antigen presentation. / Lu, C. Y.; Lemay, P. A.; Lombardi, M. J.

In: Transplantation, Vol. 45, No. 1, 1988, p. 187-194.

Research output: Contribution to journalArticle

@article{3de148371b6e4ee6a746db119c8416e3,
title = "Inhibition of antigen-specific activation of an L3T4+ T cell line by cyclosporine with maintenance of macrophage-mediated antigen presentation",
abstract = "Cyclosporine has clearly been shown to directly inhibit T lymphocyte activation by monoclonal antibodies or mitogens where nominal antigen and accessory cells are not present. However, when T lymphocytes are stimulated by antigen, as occurs in allograft rejection, T lymphocytes and accessory cells must interact with one another. Under the latter circumstances, the issue of whether cyclosporine acts on T lymphocyte, accessory cell, or both is not resolved. This issue is addressed in this study. To assess the effect of cyclosporine on T cell activation, macrophages were incubated with heat-killed Listeria and then fixed in paraformaldehyde. These fixed macrophages retained their ability to present antigen to T cells but were not affected by subsequent treatment with cyclosporine. When cyclosporine and a L3T4+ T lymphocyte line were added simultaneously to fixed, antigen-pulsed macrophages, the drug inhibited antigen-specific T cell activation with a half maximal inhibitory concentration of 10 ng/ml. To our knowledge, this is the first evidence that low doses of cyclosporine inhibit antigen-specific T cell activation where the drug's effects on antigen-presenting cells have been excluded. To assess the effects of cyclosporine on macrophage-mediated antigen-presentation, macrophages were exposed simultaneously to cyclosporine and antigen, and then fixed. Antigen-presentation was not inhibited unless extremely large doses (9000 ng/ml) of cyclosporine were used. In our experimental system, any new inhibitory activity acquired by live cyclosporine-treated macrophages could be explained by residual drug. Finally, cyclosporine did not inhibit the induction of macrophage Ia expression nor antigen-presenting function after stimulation in vitro with lymphokine.",
author = "Lu, {C. Y.} and Lemay, {P. A.} and Lombardi, {M. J.}",
year = "1988",
language = "English (US)",
volume = "45",
pages = "187--194",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Inhibition of antigen-specific activation of an L3T4+ T cell line by cyclosporine with maintenance of macrophage-mediated antigen presentation

AU - Lu, C. Y.

AU - Lemay, P. A.

AU - Lombardi, M. J.

PY - 1988

Y1 - 1988

N2 - Cyclosporine has clearly been shown to directly inhibit T lymphocyte activation by monoclonal antibodies or mitogens where nominal antigen and accessory cells are not present. However, when T lymphocytes are stimulated by antigen, as occurs in allograft rejection, T lymphocytes and accessory cells must interact with one another. Under the latter circumstances, the issue of whether cyclosporine acts on T lymphocyte, accessory cell, or both is not resolved. This issue is addressed in this study. To assess the effect of cyclosporine on T cell activation, macrophages were incubated with heat-killed Listeria and then fixed in paraformaldehyde. These fixed macrophages retained their ability to present antigen to T cells but were not affected by subsequent treatment with cyclosporine. When cyclosporine and a L3T4+ T lymphocyte line were added simultaneously to fixed, antigen-pulsed macrophages, the drug inhibited antigen-specific T cell activation with a half maximal inhibitory concentration of 10 ng/ml. To our knowledge, this is the first evidence that low doses of cyclosporine inhibit antigen-specific T cell activation where the drug's effects on antigen-presenting cells have been excluded. To assess the effects of cyclosporine on macrophage-mediated antigen-presentation, macrophages were exposed simultaneously to cyclosporine and antigen, and then fixed. Antigen-presentation was not inhibited unless extremely large doses (9000 ng/ml) of cyclosporine were used. In our experimental system, any new inhibitory activity acquired by live cyclosporine-treated macrophages could be explained by residual drug. Finally, cyclosporine did not inhibit the induction of macrophage Ia expression nor antigen-presenting function after stimulation in vitro with lymphokine.

AB - Cyclosporine has clearly been shown to directly inhibit T lymphocyte activation by monoclonal antibodies or mitogens where nominal antigen and accessory cells are not present. However, when T lymphocytes are stimulated by antigen, as occurs in allograft rejection, T lymphocytes and accessory cells must interact with one another. Under the latter circumstances, the issue of whether cyclosporine acts on T lymphocyte, accessory cell, or both is not resolved. This issue is addressed in this study. To assess the effect of cyclosporine on T cell activation, macrophages were incubated with heat-killed Listeria and then fixed in paraformaldehyde. These fixed macrophages retained their ability to present antigen to T cells but were not affected by subsequent treatment with cyclosporine. When cyclosporine and a L3T4+ T lymphocyte line were added simultaneously to fixed, antigen-pulsed macrophages, the drug inhibited antigen-specific T cell activation with a half maximal inhibitory concentration of 10 ng/ml. To our knowledge, this is the first evidence that low doses of cyclosporine inhibit antigen-specific T cell activation where the drug's effects on antigen-presenting cells have been excluded. To assess the effects of cyclosporine on macrophage-mediated antigen-presentation, macrophages were exposed simultaneously to cyclosporine and antigen, and then fixed. Antigen-presentation was not inhibited unless extremely large doses (9000 ng/ml) of cyclosporine were used. In our experimental system, any new inhibitory activity acquired by live cyclosporine-treated macrophages could be explained by residual drug. Finally, cyclosporine did not inhibit the induction of macrophage Ia expression nor antigen-presenting function after stimulation in vitro with lymphokine.

UR - http://www.scopus.com/inward/record.url?scp=0023864797&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023864797&partnerID=8YFLogxK

M3 - Article

VL - 45

SP - 187

EP - 194

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 1

ER -