Interleukin 2 induction of proliferation in resting T lymphocytes requires contact with monocytes

Resting human T cells are known to express significant numbers of intermediate but none or barely detectable low and high affinity IL-2 receptors (IL-2R). IL-2 alone failed to induce proliferation in these cells. However, in presence of small proportion of autologous monocytes, as low as 22 pM, IL-2 induced high levels of proliferation in resting T cells. Introduction of a semi permeable membrane between the two cell types or addition of an anti-CD11b mAb inhibited such induction of proliferation by IL-2. Neither recombinant IL-1 nor IL-1-containing cell-free extracts from activated monocytes substituted for intact monocytes. Autologous B cells failed to replace monocytes. Using antigen-specific cloned human T cells we have shown a lack of requirement for antigen. The proliferation was inhibited by anti-IL-2R alpha mAb. IL-2 appears to be unique since neither IL-4 nor IL-6, alone or in presence of monocytes, led to induction of proliferation in resting T cells. Combination of IL-2 and monocytes induced proliferation in all T cell subpopulations (CD4+, CD8+, CD45RA+ and CD45RO+) and antigen-specific clones examined. It also induces mRNA and surface expression of IL-2R alpha, appearance of high affinity IL-2R and induction of proliferation in large proportions of T cells. As in humans, the IL-2 induction of proliferation in murine resting T cells required contact with syngeneic monocytes, suggesting that such a mechanism of T cells activation is highly conserved.