HLA-DR human histocompatibility leukocyte antigens-restricted lymphocyte-monocyte interactions in the release from monocytes of acidic isoferritins that suppress hematopoietic progenitor cells

Hal Broxmeyer, L. Juliano, L. Lu, E. Platzer, B. Dupont

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Abstract

Acidic isoferritins, which under normal conditions are released from monocytes and macrophages, have a suppressive effect in vitro on granulocyte-macrophage, erythroid, and multipotential hematopoietic progenitor cells. Cell interactions modulating the release of acidic isoferritin-inhibitory activity (AIFIA) from human monocytes were investigated using the bone marrow granulocyte-macrophage progenitor cells as a target cell assay for assessing AIFIA. Monocytes, in the absence of T lymphocytes, released AIFIA when allowed to condition culture medium at 104 or higher concentrations of monocytes/ml. However, subpopulations of T lymphocytes modulated the release of AIFIA from monocytes. OKT8+- and OKT4+-T lymphocytes were obtained from E-rosette-positive lymphocytes by using T lymphocyte subset-specific monoclonal antibodies in either a complement-dependent cytotoxicity test to select negatively for the cells or by selection using a 'panning' procedure. OKT8+-T lymphocytes suppressed completely and OKT4+-T lymphocytes enhanced the constitutive release of AIFIA from monocytes. OKT4+ lymphocytes also induced the release of AIFIA from concentrations of 103 monocytes/ml which did not release measurable amounts of AIFIA by themselves. The release of AIFIA from monocytes involved HLA-DR+-monocytes and -T lymphocytes. Pulsing monocytes with monoclonal antibodies to framework determinants on HLA-Dr molecules, in the absence of complement, did not influence the constitutive release of AIFIA. Pulsing monocytes or T lymphocyte subpopulations with such antibodies, in the absence of complement, blocked the suppressing and inducing activities of the appropriate subpopulations of T lymphocytes. Monoclonal antibodies to common determinants shared by HLA-A, B, and C molecules did not block these cellular interactions. Treating monocytes and T lymphocytes in a complement-dependent cytotoxicity test with dilutions of the anti-HLA-DR antibodies that did not block the cellular interactions removed the populations of monocytes constitutively releasing AIFIA and the T lymphocyte subsets modulating this release. Modulation of the release of AIFIA from monocytes by T lymphocyte subpopulations required the use of autologous cells, cells from HLA-identical siblings, or unrelated donors matched for HLA-DR. Matching for only one HLA haplotype gave partial responses and this was seen in testing cells from related individuals as well as among unrelated test combinations. These cellular interactions were not detected with HLA-DR-incompatible cells differing for two HLA-DR antigens. Admixture of such HLA-DR-incompatible allogeneic cells did not interfere with the regulation of AIFIA release in the autologous cell interactions. Thus, release of AIFIA from monocytes is restricted genetically by HLA-DR at the level of T lymphocyte-monocyte interactions. The genetic determinants on the HLA-class II molecules that induce stimulation in vitro in mixed lymphocyte culture (i.e., HLA-D), however, were not involved in this effort.

Original languageEnglish (US)
Pages (from-to)939-953
Number of pages15
JournalJournal of Clinical Investigation
Volume73
Issue number4
StatePublished - 1984
Externally publishedYes

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Histocompatibility Antigens
HLA-DR Antigens
HLA Antigens
Hematopoietic Stem Cells
Monocytes
Lymphocytes
T-Lymphocytes
acidic isoferritin
Monoclonal Antibodies
Lymphocyte Subsets
T-Lymphocyte Subsets
Cell Communication
Macrophages
HLA-C Antigens
HLA-D Antigens
Unrelated Donors
Granulocyte-Macrophage Progenitor Cells
HLA-A Antigens
HLA-B Antigens
Antibodies

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{753e7fbc9e574828b846079a55f260fd,
title = "HLA-DR human histocompatibility leukocyte antigens-restricted lymphocyte-monocyte interactions in the release from monocytes of acidic isoferritins that suppress hematopoietic progenitor cells",
abstract = "Acidic isoferritins, which under normal conditions are released from monocytes and macrophages, have a suppressive effect in vitro on granulocyte-macrophage, erythroid, and multipotential hematopoietic progenitor cells. Cell interactions modulating the release of acidic isoferritin-inhibitory activity (AIFIA) from human monocytes were investigated using the bone marrow granulocyte-macrophage progenitor cells as a target cell assay for assessing AIFIA. Monocytes, in the absence of T lymphocytes, released AIFIA when allowed to condition culture medium at 104 or higher concentrations of monocytes/ml. However, subpopulations of T lymphocytes modulated the release of AIFIA from monocytes. OKT8+- and OKT4+-T lymphocytes were obtained from E-rosette-positive lymphocytes by using T lymphocyte subset-specific monoclonal antibodies in either a complement-dependent cytotoxicity test to select negatively for the cells or by selection using a 'panning' procedure. OKT8+-T lymphocytes suppressed completely and OKT4+-T lymphocytes enhanced the constitutive release of AIFIA from monocytes. OKT4+ lymphocytes also induced the release of AIFIA from concentrations of 103 monocytes/ml which did not release measurable amounts of AIFIA by themselves. The release of AIFIA from monocytes involved HLA-DR+-monocytes and -T lymphocytes. Pulsing monocytes with monoclonal antibodies to framework determinants on HLA-Dr molecules, in the absence of complement, did not influence the constitutive release of AIFIA. Pulsing monocytes or T lymphocyte subpopulations with such antibodies, in the absence of complement, blocked the suppressing and inducing activities of the appropriate subpopulations of T lymphocytes. Monoclonal antibodies to common determinants shared by HLA-A, B, and C molecules did not block these cellular interactions. Treating monocytes and T lymphocytes in a complement-dependent cytotoxicity test with dilutions of the anti-HLA-DR antibodies that did not block the cellular interactions removed the populations of monocytes constitutively releasing AIFIA and the T lymphocyte subsets modulating this release. Modulation of the release of AIFIA from monocytes by T lymphocyte subpopulations required the use of autologous cells, cells from HLA-identical siblings, or unrelated donors matched for HLA-DR. Matching for only one HLA haplotype gave partial responses and this was seen in testing cells from related individuals as well as among unrelated test combinations. These cellular interactions were not detected with HLA-DR-incompatible cells differing for two HLA-DR antigens. Admixture of such HLA-DR-incompatible allogeneic cells did not interfere with the regulation of AIFIA release in the autologous cell interactions. Thus, release of AIFIA from monocytes is restricted genetically by HLA-DR at the level of T lymphocyte-monocyte interactions. The genetic determinants on the HLA-class II molecules that induce stimulation in vitro in mixed lymphocyte culture (i.e., HLA-D), however, were not involved in this effort.",
author = "Hal Broxmeyer and L. Juliano and L. Lu and E. Platzer and B. Dupont",
year = "1984",
language = "English (US)",
volume = "73",
pages = "939--953",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "4",

}

TY - JOUR

T1 - HLA-DR human histocompatibility leukocyte antigens-restricted lymphocyte-monocyte interactions in the release from monocytes of acidic isoferritins that suppress hematopoietic progenitor cells

AU - Broxmeyer, Hal

AU - Juliano, L.

AU - Lu, L.

AU - Platzer, E.

AU - Dupont, B.

PY - 1984

Y1 - 1984

N2 - Acidic isoferritins, which under normal conditions are released from monocytes and macrophages, have a suppressive effect in vitro on granulocyte-macrophage, erythroid, and multipotential hematopoietic progenitor cells. Cell interactions modulating the release of acidic isoferritin-inhibitory activity (AIFIA) from human monocytes were investigated using the bone marrow granulocyte-macrophage progenitor cells as a target cell assay for assessing AIFIA. Monocytes, in the absence of T lymphocytes, released AIFIA when allowed to condition culture medium at 104 or higher concentrations of monocytes/ml. However, subpopulations of T lymphocytes modulated the release of AIFIA from monocytes. OKT8+- and OKT4+-T lymphocytes were obtained from E-rosette-positive lymphocytes by using T lymphocyte subset-specific monoclonal antibodies in either a complement-dependent cytotoxicity test to select negatively for the cells or by selection using a 'panning' procedure. OKT8+-T lymphocytes suppressed completely and OKT4+-T lymphocytes enhanced the constitutive release of AIFIA from monocytes. OKT4+ lymphocytes also induced the release of AIFIA from concentrations of 103 monocytes/ml which did not release measurable amounts of AIFIA by themselves. The release of AIFIA from monocytes involved HLA-DR+-monocytes and -T lymphocytes. Pulsing monocytes with monoclonal antibodies to framework determinants on HLA-Dr molecules, in the absence of complement, did not influence the constitutive release of AIFIA. Pulsing monocytes or T lymphocyte subpopulations with such antibodies, in the absence of complement, blocked the suppressing and inducing activities of the appropriate subpopulations of T lymphocytes. Monoclonal antibodies to common determinants shared by HLA-A, B, and C molecules did not block these cellular interactions. Treating monocytes and T lymphocytes in a complement-dependent cytotoxicity test with dilutions of the anti-HLA-DR antibodies that did not block the cellular interactions removed the populations of monocytes constitutively releasing AIFIA and the T lymphocyte subsets modulating this release. Modulation of the release of AIFIA from monocytes by T lymphocyte subpopulations required the use of autologous cells, cells from HLA-identical siblings, or unrelated donors matched for HLA-DR. Matching for only one HLA haplotype gave partial responses and this was seen in testing cells from related individuals as well as among unrelated test combinations. These cellular interactions were not detected with HLA-DR-incompatible cells differing for two HLA-DR antigens. Admixture of such HLA-DR-incompatible allogeneic cells did not interfere with the regulation of AIFIA release in the autologous cell interactions. Thus, release of AIFIA from monocytes is restricted genetically by HLA-DR at the level of T lymphocyte-monocyte interactions. The genetic determinants on the HLA-class II molecules that induce stimulation in vitro in mixed lymphocyte culture (i.e., HLA-D), however, were not involved in this effort.

AB - Acidic isoferritins, which under normal conditions are released from monocytes and macrophages, have a suppressive effect in vitro on granulocyte-macrophage, erythroid, and multipotential hematopoietic progenitor cells. Cell interactions modulating the release of acidic isoferritin-inhibitory activity (AIFIA) from human monocytes were investigated using the bone marrow granulocyte-macrophage progenitor cells as a target cell assay for assessing AIFIA. Monocytes, in the absence of T lymphocytes, released AIFIA when allowed to condition culture medium at 104 or higher concentrations of monocytes/ml. However, subpopulations of T lymphocytes modulated the release of AIFIA from monocytes. OKT8+- and OKT4+-T lymphocytes were obtained from E-rosette-positive lymphocytes by using T lymphocyte subset-specific monoclonal antibodies in either a complement-dependent cytotoxicity test to select negatively for the cells or by selection using a 'panning' procedure. OKT8+-T lymphocytes suppressed completely and OKT4+-T lymphocytes enhanced the constitutive release of AIFIA from monocytes. OKT4+ lymphocytes also induced the release of AIFIA from concentrations of 103 monocytes/ml which did not release measurable amounts of AIFIA by themselves. The release of AIFIA from monocytes involved HLA-DR+-monocytes and -T lymphocytes. Pulsing monocytes with monoclonal antibodies to framework determinants on HLA-Dr molecules, in the absence of complement, did not influence the constitutive release of AIFIA. Pulsing monocytes or T lymphocyte subpopulations with such antibodies, in the absence of complement, blocked the suppressing and inducing activities of the appropriate subpopulations of T lymphocytes. Monoclonal antibodies to common determinants shared by HLA-A, B, and C molecules did not block these cellular interactions. Treating monocytes and T lymphocytes in a complement-dependent cytotoxicity test with dilutions of the anti-HLA-DR antibodies that did not block the cellular interactions removed the populations of monocytes constitutively releasing AIFIA and the T lymphocyte subsets modulating this release. Modulation of the release of AIFIA from monocytes by T lymphocyte subpopulations required the use of autologous cells, cells from HLA-identical siblings, or unrelated donors matched for HLA-DR. Matching for only one HLA haplotype gave partial responses and this was seen in testing cells from related individuals as well as among unrelated test combinations. These cellular interactions were not detected with HLA-DR-incompatible cells differing for two HLA-DR antigens. Admixture of such HLA-DR-incompatible allogeneic cells did not interfere with the regulation of AIFIA release in the autologous cell interactions. Thus, release of AIFIA from monocytes is restricted genetically by HLA-DR at the level of T lymphocyte-monocyte interactions. The genetic determinants on the HLA-class II molecules that induce stimulation in vitro in mixed lymphocyte culture (i.e., HLA-D), however, were not involved in this effort.

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