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The Role of Macrophages in Thymocyte Mitogenesis

Gordon Mills, Vicky Monticone and Verner Paetkau
J Immunol October 1, 1976, 117 (4) 1325-1330;
Gordon Mills
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Vicky Monticone
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Verner Paetkau
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Abstract

The thymic lymphocytes of CBA/J mice respond to the mitogen Concanavalin A (Con A) only in the presence of adherent cells of the monocyte-macrophage series. Depletion of adherent cells abrogates the response, and macrophage-rich populations of cells restore it. The need for macrophages and mitogen is completely provided by irradiated splenic macrophages which have been exposed to Con A and washed free of the soluble mitogen. The mitogenmacrophage effect in this case is apparently not due to soluble factors.

Even more striking than the effect of macrophages on fresh cultures of thymic lymphocytes is their ability to restimulate quiescent cells 72 hr after their first stimulation with Con A. The quiescent cells respond immediately and quantitatively to Con A in the presence of fresh macrophages. This stimulation, like that of fresh thymocytes, is also controlled by a lymphokine (“costimulator”) produced by mixing macrophages, mitogen, and T lymphocytes.

Our data suggest a model in which two signals are required for mitogenesis. First, the interaction of macrophage, T cell, and mitogen elicits a soluble costimulator, which is itself not mitogenic. Secondly, in the presence of costimulator, the mitogen (either soluble, or, more efficiently, bound to macrophages) induces a proliferative response in the T cell.

Footnotes

  • ↵2 G. M. received a Vessie Heckbert Memorial Fellowship.

  • ↵3 Please address correspondence to Verner Paetkau.

  • ↵1 This work was supported by grants from NCI and MRC of Canada.

  • Received April 6, 1976.
  • Copyright © 1976 by The American Association of Immunologists, Inc.

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The Journal of Immunology
Vol. 117, Issue 4
1 Oct 1976
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The Role of Macrophages in Thymocyte Mitogenesis
Gordon Mills, Vicky Monticone, Verner Paetkau
The Journal of Immunology October 1, 1976, 117 (4) 1325-1330;

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The Role of Macrophages in Thymocyte Mitogenesis
Gordon Mills, Vicky Monticone, Verner Paetkau
The Journal of Immunology October 1, 1976, 117 (4) 1325-1330;
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Print ISSN 0022-1767        Online ISSN 1550-6606