The role of interleukin-6 in mitogenic T-cell activation: detection of interleukin-2 heteronuclear RNA by polymerase chain reaction.
It has been documented that interleukin-6 (IL-6) supports the proliferation of purified, anti-CD3-stimulated murine T cells. We found that stimulation of human peripheral blood mononuclear cells (PBMCs) with anti-CD3 induced a significant accumulation of IL-6 mRNA, indicating that antigen-mediated T-cell activation may involve IL-6 release from accessory cells. Phytohemagglutinin (PHA) had little effect upon IL-6 gene expression. In keeping with these findings, anti-IL-6 reduced but did not abolish anti-CD3-mediated proliferation of PBMCs, but had no significant effect upon PHA-stimulated proliferation. The addition of recombinant (r) IL-6 enhanced the proliferation of anti-CD3-stimulated PBMCs and increased the accumulation of IL-2 mRNA in PHA-stimulated PBMCs during the first 5 hr of culture. Nuclear run-off experiments did not reveal significant changes in IL-2 transcription in PHA plus rIL-6-treated PBMCs attempting to assume that IL-6 mediates stabilization of IL-2 mRNA. However, monitoring of partially spliced IL-2 mRNA by polymerase chain reaction revealed a clear increase in IL-2 heteronuclear RNA. Thus IL-6 increases the rate of IL-2 transcription which was not detectable by conventional in vitro transcription assays. We conclude that anti-CD3 triggers T-cell proliferation through a process that is partially but not entirely dependent upon release of IL-6. IL-6, in turn, supports IL-2 transcription. Insofar as anti-CD3 mimics antigen-triggered activation of the T-cell receptor complex, IL-6 appears to support the early immune response by augmenting antigen-triggered IL-2 gene expression.
Walz
G
G
Department of Medicine, Beth Israel Hospital, Boston, Massachusetts.
Stevens
C
C
Zanker
B
B
Melton
L B
LB
Clark
S C
SC
Suthanthiran
M
M
Strom
T B
TB
D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D001483:Base Sequence; D017252:CD3 Complex; D002478:Cells, Cultured; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D015850:Interleukin-6 / Q000032:analysis / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D015850:Interleukin-6; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins