Interleukin-12 activates human gamma delta T cells: synergistic effect of tumor necrosis factor-alpha.
gammadelta T cell populations are known to expand in response to intracellular bacterial infectious agents regardless of previous priming. We have shown previously that soluble factor(s) produced by Mycobacterium-stimulated monocytes activate cord blood gammadelta T cells to proliferate. In this study, we investigated whether cytokines produced by monocytes are responsible for gammadelta T cell activation in vitro: interleukin (IL)-1beta, IL-6, IL-8, IL-12, tumor necrosis factor (TNF)-alpha and granulocyte/macrophage colony-stimulating factor were examined. Recombinant human IL-12 stimulated gammadelta T cells, but not alphabeta T cells in peripheral blood mononuclear cells, to express CD25 on their surfaces, and to expand in number in vitro. IL-12-primed gammadelta T cell numbers increased to a greater extent in the culture to which exogenous IL-2 (5 U/ml) was added. Anti-TNF-alpha monoclonal antibody inhibited IL-12-induced up-regulation of CD25 on gammadelta T cells, suggesting that endogenous TNF-alpha may play a role in IL-12-induced activation of gammadelta T cells. Recombinant TNF-alpha synergistically augmented IL-12-induced activation of gammadelta T cells. Furthermore, IL-12 up-regulated TNF receptors on gammadelta T cells in vitro: TNF-alpha binding to its receptor induced CD25 expression on the gammadelta T cells in an autocrine or paracrine fashion, or perhaps both. It also became evident that both IL-12 and TNF-alpha were produced by mycobacterial lysate-stimulated monocytes. Taken together, these results suggest that upon confrontation with mycobacterial organisms, gammadelta T cells can be quickly and antigen-nonspecifically activated by soluble factors including IL-12 and TNF-alpha, both of which are produced by mononuclear phagocytes in response to mycobacterial organisms.
Ueta
C
C
Osaka Prefectural Habikino Hospital, Japan.
Kawasumi
H
H
Fujiwara
H
H
Miyagawa
T
T
Kida
H
H
Ohmoto
Y
Y
Kishimoto
S
S
Tsuyuguchi
I
I
D000328:Adult; D001426:Bacterial Proteins / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009161:Mycobacterium / Q000472:pathogenicity; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology*
D001426:Bacterial Proteins; D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12