Interaction of lactoferrin, monocytes, and T lymphocyte subsets in the regulation of steady-state granulopoiesis in vitro

G. C. Bagby, V. D. Rigas, Robert (Rob) Bennett, Arthur Vandenbark, H. S. Garewal

Research output: Contribution to journalArticle

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Abstract

Colony-stimulating activities (CSA) are potent granulopoietic stimulators in vitro. Using clonogenic assay techniques, we analyzed the degree to which mononuclear phagocytes and T lymphocytes cooperate in the positive (production/release of CSA) and feedback (inhibition of CSA production/release) regulation of granulopoiesis. We measured the effect of lactoferrin (a putative feedback regulator of CSA production) on CSA provision in three separate assay systems wherein granulocyte colony growth of marrow cells from 22 normal volunteers was stimulated by endogenous CSA-producing cells in the marrow cell suspension, autologous peripheral blood leukocytes in feeder layers, and medium conditioned by peripheral blood leukocytes. The CSA-producing cell populations in each assay were varied by using cell separation techniques and exposure of isolated T lymphocytes to methylprednisolone or to monoclonal antibodies to surface antigens and complement. We noted that net CSA production increased more than twofold when a small number of unstimulated T lymphocytes were added to monocyte cultures. Lactoferrin's inhibitory effect was also T lymphocyte dependent. The T lymphocytes that interact with monocytes and lactoferrin to inhibit CSA production are similar to those that augment CSA production because their activities are neither genetically restricted nor glucocorticoid sensitive, and both populations express HLA-DR (Ia-like) and T3 antigens but not T4 or T8 antigens. These findings are consistent with results of our studies on the mechanism of lactoferrin's inhibitory effect which indicate that mononuclear phagocytes produce both CSA and soluble factors that stimulate T lymphocytes to produce CSA, and that lactoferrin does not suppress monocyte CSA production, but does completely suppress production or release by monocytes of those factors that stimulate T lymphocytes to produce CSA. We conclude that mononuclear phagocytes and a subset of T lymphocytes exhibit important complex interactions in the regulation of granulopoiesis.

Original languageEnglish (US)
Pages (from-to)56-63
Number of pages8
JournalJournal of Clinical Investigation
Volume68
Issue number1
StatePublished - 1981
Externally publishedYes

Fingerprint

Lactoferrin
T-Lymphocyte Subsets
Monocytes
T-Lymphocytes
Phagocytes
Leukocytes
Bone Marrow
CD3 Antigens
Feeder Cells
Cell Separation
Histocompatibility Antigens Class II
Methylprednisolone
HLA-DR Antigens
Vulnerable Populations
Surface Antigens
Conditioned Culture Medium
In Vitro Techniques
Granulocytes
Glucocorticoids
Suspensions

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Interaction of lactoferrin, monocytes, and T lymphocyte subsets in the regulation of steady-state granulopoiesis in vitro. / Bagby, G. C.; Rigas, V. D.; Bennett, Robert (Rob); Vandenbark, Arthur; Garewal, H. S.

In: Journal of Clinical Investigation, Vol. 68, No. 1, 1981, p. 56-63.

Research output: Contribution to journalArticle

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