The CD2 and CD28 adhesion molecules induce long‐term autocrine proliferation of CD4+ T cells

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Abstract
In vitro human T lymphocyte activation requires two‐signal triggering delivered by lectins, phorbol esters or antibodies directed against surface molecules. Stimulation of adhesion molecules by CD2 and/or CD28 antibodies defines alternative activation pathways. Activation by CD2 + CD28 monoclonal antibodies induces high‐level, long‐lasting and monocyte‐independent proliferation of highly purified T cells. Limiting dilution cultures showed that CD28 in association with CD2 or CD3, without addition of exogenous cytokines, induced single‐cell proliferation. CD2 + CD28 stimulation induced long‐term interleukin (IL)‐2‐dependent autocrine proliferation of CD4+ T cell clones. We tried to elucidate this long‐term proliferation by evaluating cytokine secretion and cytokine dependency. CD28 associated to CD3 or CD2 induced high levels of IL‐2, tumor necrosis factor (TNF) and IL‐4 secretion for 10 days, in contrast to CD3 alone which induced only TNF secretion. Cytokines of the monocytic lineage were also secreted, such as colony‐stimulating factor‐1, granulocyte macrophage colony‐stimulating factor or IL‐1, the latter being more specific of CD2 + CD28 activation. Blocking antibodies confirmed the crucial role of IL‐2 in CD2 + CD28 activation. Anti‐IL‐4, anti‐IL‐7 receptor or anti‐TNF antibodies had no effect on proliferation. Stimulation with CD2 + CD28 induced long‐term autocrine (at least for IL‐2) proliferation for CD4+ T cells, with no evidence for the implication of another cytokine among those tested other than IL‐2. This represents a model for long‐term autocrine growth for non‐leukemic cells.

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