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Crowding-Dependent Production of Colony-Stimulating Factors by Cultured Syngeneic or Allogeneic Hematopoietic Cells
Donald Metcalf, Ladina Di Rago and Sandra Mifsud
Proceedings of the National Academy of Sciences of the United States of America
Vol. 100, No. 3 (Feb. 4, 2003), pp. 1244-1249
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/3138317
Page Count: 6
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Mitogenic stimulation in vitro of mouse T lymphocytes induces the production of the hematopoietic cytokines granulocyte-macrophage colony-stimulating factor and IL-3. The present experiments showed that simple crowding of murine spleen or lymph node cells was a sufficient inducing stimulus. Crowding did not have this consequence for thymus or marrow cells or spleen cells from nu/nu or Rag-1-/- mice lacking T lymphocytes. Crowding for as short a period as 24 h was sufficient to allow subsequent cytokine production in sparse cultures. Purified T lymphocytes also exhibited low levels of crowding induction of cytokine production and cytokine production was enhanced by IL-2 and IFN-γ. However, IFN-γ-/- spleen cells exhibited similar crowding-induced colony-stimulating factor production to that of control spleen cells. Excess cell crowding inhibited cytokine production. This inhibition was not caused by receptor internalization of cytokines but may contribute to the failure to observe IL-3 production in lymphoid organs in vivo. Coculture of allogeneic spleen or peritoneal cells was a strong inducing signal for colony-stimulating factor production but this parameter was unable to detect autoreactivity of T lymphocytes in mice that lack suppressor of cytokine signaling 1 and exhibit T lymphocyte activation.
Proceedings of the National Academy of Sciences of the United States of America © 2003 National Academy of Sciences