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RESEARCH PRODUCT

Functional Analysis of Alloreactive Helper T Cells Involved in the Induction of Cytolytic T Cell Responses In Vitro

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When T-responder cells are sensitized in vitro to foreign antigen presented on syngeneic cells or towards allogeneic stimulator cells, a proliferative response is initiated in which antigen specific cytotoxic T lymphocytes (CTL) are generated. The induction of CTL, however, requires the collaboration between functionally distinct T cell subpopulations1–5 and accessory cells from the macrophage lineage, including dendritic cells. The experimental data accumulated so far reveal a cascade of T-T cell interactions and distinct functions of their soluble products resulting in the “Interleukin concept”6 (Fig. 1). Upon receptor-antigen interaction, the “antigen-selected” clones of CTLp become sensitive to helper factors such as Interleukin-2 (IL-2).7 Il-2 binds to non-clonally distributed receptors on sensitized CTLp clones and thus induces CTL-P to proliferate. Their differentiation into cytolytic effector cells, however, requires another soluble helper factor, distinct from Il-2 and provisionally named cytotoxic T cell differentiation factor (CTDF).8,9 As with CTLp the activation of HTL-precursors (THTLp) also requires the appropriate antigen recognition by clonally distributed receptors. Upon binding to antigen the antigen selected HTL clones become sensitive to the inductive effect of Interleukin-1 (Il-1).