Crowding-dependent production of colony-stimulating factors by cultured syngeneic or allogeneic hematopoietic cells.
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-gamma. However, IFN-gamma-/- 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.
Metcalf
Donald
D
Division of Cancer and Hematology, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, 3050 Victoria, Australia. metcalf@wehi.edu.au
Di Rago
Ladina
L
Mifsud
Sandra
S
D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis; D018929:Cell Culture Techniques / Q000379:methods*; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007377:Interleukin-3 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D008822:Mice, Transgenic; D012097:Repressor Proteins; D013154:Spleen / Q000166:cytology*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013601:T-Lymphocytes / Q000166:cytology; D013997:Time Factors
D002352:Carrier Proteins; D007377:Interleukin-3; D012097:Repressor Proteins; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor