Interleukin-10 downregulates proliferation and expression of interleukin-2 receptor p55 chain and interferon-gamma, but not interleukin-2 or interleukin-4, by parasite-specific helper T cell clones obtained from cattle chronically infected with Babesia bovis or Fasciola hepatica.
Human recombinant interleukin-10 (IL-10) was previously shown to inhibit accessory cell (AC)-dependent proliferation of bovine parasite-specific T helper 1 (Th1), Th2, and Th0 cells in an IL-2-reversible manner (Brown, W.C., Woods, V.M., Chitko-McKown, C.G., Hash, S.M., and Rice-Ficht, A.C., 1994. Infect. Immun. 62, 4697-4708). The present study was therefore designed to determine whether the effect of IL-10 on T cell proliferation corresponded with downregulated expression of cytokines, or their receptors, important for T cell growth. The effects of IL-10 on cellular proliferation and expression of IL-2, IL-4, IL-2 receptor (IL-2R; p55), and IFN-gamma by Babesia bovis- or Fasciola hepatica-specific Th cell clones were simultaneously evaluated. As shown previously, IL-10 strongly inhibited proliferation of all types of Th cell clones, although this did not correspond with reduced expression of IL-2 or IL-4 mRNA or their products. In contrast, expression of IL-2R mRNA was consistently reduced in the IL-10-treated clones. These results indicate that IL-10 does not inhibit AC-dependent proliferation of bovine Th cells by downregulating T cell cytokines; rather, IL-10 may act by downregulating IL-2R p55 expression and subsequent signal transduction leading to decreased cellular proliferation. IFN-gamma production was also consistently downregulated in the presence of IL-10.
Chitko-McKown
C G
CG
Department of Veterinary Pathobiology, Texas A&M University, College Station 77843, USA.
Ruef
B J
BJ
Rice-Ficht
A C
AC
Brown
W C
WC
D000818:Animals; D001404:Babesiosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D002999:Clone Cells; D015536:Down-Regulation; D005211:Fascioliasis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000494:pharmacology; D007378:Interleukins / Q000096:biosynthesis / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000737:chemistry; D011994:Recombinant Proteins / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000469:parasitology
D007378:Interleukins; D010446:Peptide Fragments; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D016753:Interleukin-10; D007371:Interferon-gamma