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CD40–CD40 ligand (CD154) engagement is required but may not be sufficient for human T helper 1 cell induction of interleukin‐2‐ or interleukin‐15‐driven, contact‐dependent, interleukin‐1β production by monocytes
Author(s) -
Ribbens C.,
Dayer J.M.,
Chizzolini C.
Publication year - 2000
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2000.00948.x
Subject(s) - cd40 , cd154 , monocyte , biology , interleukin 10 , t cell , interleukin , interleukin 4 , interleukin 2 , microbiology and biotechnology , immunology , cytokine , immune system , cytotoxic t cell , biochemistry , in vitro
Summary To investigate whether antigen‐independent, interleukin‐2 (IL‐2) or IL‐15 activation of polarized T helper (Th) cells would result in contact‐dependent activation of monocytes, living Th1 and Th2 cell clones were co‐cultured with THP‐1 cells or fresh peripheral blood monocytes. Under these conditions IL‐1β production was induced almost exclusively by Th1 cells and was dependent on the presence and dose of IL‐2 or IL‐15, and on cell–cell contact, as demonstrated by double‐chamber cultures. Low levels of IL‐1 receptor antagonist (IL‐1Ra) were induced by Th1 and higher levels by Th2 cells. IL‐10 production was similar in Th1/monocyte and Th2/monocyte co‐cultures, thus arguing against preferential down‐regulation of IL‐1β production by anti‐inflammatory IL‐10 in Th2 co‐cultures. In addition, IL‐4 and IL‐10 neutralization did not result in enhanced IL‐1β production in Th2/monocyte co‐cultures. Preferential expression on Th1 cells of CD11b correlated with their capacity to induce IL‐1β production by THP‐1 cells in the presence of IL‐2 or IL‐15, but anti‐CD11b monoclonal antibody could not inhibit this activity. Blockade of the CD40–CD40 ligand interaction resulted in inhibition of IL‐1β‐inducing capacity while IL‐1Ra induction was unaffected, a result previously unknown. This differential effect indicates the selective relevance of CD40–CD40 ligand engagement in inflammatory monocyte responses upon activation by T cells. CD40 ligand expression levels did not differ in Th1 and Th2 cell clones, thus indicating that additional, unidentified molecule(s) preferentially expressed by Th1 cells are involved in their IL‐1β induction capacity.