Recombinant granulocyte-macrophage colony-stimulating factor restores deficient immune responses in mice with chronic Trypanosoma cruzi infections.
Spleen cells from mice with chronic Trypanosoma cruzi infection generate a minimal plaque-forming response to SRBC in vitro. Addition of granulocyte-macrophage (GM)-CSF to cultures of spleen cells from chronically infected mice restored the plaque-forming cells (PFC) response to normal levels. Splenic adherent cells from chronically infected mice were deficient in their ability to reconstitute the PFC response of accessory cell-depleted normal spleen cells. Preincubation of splenic adherent cells from infected mice with GM-CSF restored their ability to reconstitute the PFC response of adherent cell depleted cultures. Ia Ag expression by splenic adherent cells from chronically infected mice was significantly lower compared to Ia Ag expression of cells from normal mice. Incubation of splenic adherent cells from chronically infected mice for 48 h with GM-CSF increased levels of Ia Ag expression to approximately those of uninfected mice. Peritoneal macrophages from infected mice produced IL-1 after incubation with GM-CSF at levels equivalent to those produced by similarly treated control macrophages. Spleen cells from chronically infected mice showed significant induction of IL-2 mRNA after GM-CSF treatment, and the addition of the anti-IL-2 mAb to GM-CSF supplemented cultures of spleen cells from infected mice blocked the restoration of the anti-SRBC PFC response. Thus, the ability of GM-CSF to restore the anti-PFC response to SRBC appears to involve the up-regulation of accessory cell function that includes increased Ia Ag expression and the induction of IL-1 production. These events also involve increased IL-2 production with resultant up-regulation of the response to SRBC by spleen cells from infected mice. Finally, it was shown that treatment of infected mice with rGM-CSF completely restored their depressed PFC production in vivo.
Reed
S G
SG
Seattle Biomedical Research Institute, WA 98109.
Grabstein
K H
KH
Pihl
D L
DL
Morrissey
P J
PJ
D000818:Animals; D000917:Antibody Formation; D000938:Antigen-Presenting Cells / Q000276:immunology; D015152:Blotting, Northern; D014355:Chagas Disease / Q000276:immunology*; D002908:Chronic Disease; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010529:Peritoneal Cavity / Q000166:cytology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014349:Trypanosoma cruzi
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor