Interleukin‐10‐induced CD8 cell proliferation

Authors:
  • MLM W Lepper
    M W Lepper
  • RGR J Garland
    R J Garland
  • CCC V Cox
    C V Cox
  • ECE G Corley
    E G Corley
  • AOA Oakhill
    A Oakhill
  • CSC G Steward
    C G Steward
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Abstract
Interleukin (IL)‐10, a product of T helper 2 (Th2) lymphocytes, has been shown to be an important regulator of lymphoid and myeloid cells, inhibiting mitogen, peptide and alloantigen‐induced T‐cell proliferation and IL‐2 production. The microenvironment at the time of cell activation, notably the presence or absence of cytokines such as IL‐10, interferon‐γ (IFN‐γ) and IL‐2, is believed to determine the lineage and magnitude of cell‐mediated responses. In this study, we show that recombinant human IL‐10 (rhIL‐10) exerts a dose‐dependent inhibitory effect on human peripheral blood mononuclear cells stimulated in vitro, when these cells have not previously been exposed to rhIL‐10. Furthermore, incubation of these cells with high doses of rhIL‐10, either before or at the time of activation, results in inhibition which is followed several days later by the emergence of a population of CD8 positive cells. This rhIL‐10‐responsive CD8, positive cell population still emerges even when the cells are washed following incubation with rhIL‐10 prior to cell activation. Using purified CD8 populations this was shown to be a direct action of rhIL‐10 on CD8 cells and not via CD4 positive cells and monocytes. This finding was only observed when cells were activated with a cross‐linking anti‐CD3 antibody and not when activated with phorbol‐12‐mystrate‐13‐acetate (PMA) and calcium ionophore (CaIon), suggesting that the effect is mediated through cell‐surface receptors. Analysis of CD8 positive clones reveal production of Tc2 patterns of cytokines and reduced cell cytotoxicity to allogeneic, natural killer and lymphokine activated cell targets.

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