Characterization of primary T helper cell activation and T helper cell lines stimulated by hapten-modified, cultured Langerhans cells.

It has recently been shown that hapten-modified cultured Langerhans cells are able to activate small resting syngeneic L3T4+ T helper cells from nonsensitized animals. Repeated stimulation of these T cells with hapten-modified cultured Langerhans cells leads to the establishment of L3T4+ hapten-specific interleukin-4-producing T-cell lines. Here we report on further characteristics of primary hapten-dependent activation of L3T4+ T cells and of T-cell lines derived from them. Dendritic cell-enriched spleen cells were as able as Langerhans cells to activate nonsensitized T helper cells after hapten modification. However, M12c, a major histocompatibility complex class II-positive B-cell line that was able to activate small, resting, allogeneic L3T4+ T cells was not able to stimulate syngeneic T helper cells after hapten modification. Thy1+ dendritic epidermal cells did not significantly affect the magnitude of primary T helper cell proliferation induced by cultured Langerhans cells. Restimulation of in vitro primed T helper cells with hapten-modified cultured Langerhans cells revealed the presence, within the primed T helper cell population, of activated cells with specificity to an unrelated hapten, suggesting that, in hapten-dependent T helper cell activation, hapten-nonspecific cells are activated along with those that are hapten specific. Restimulation of a hapten-specific long-term T helper cell subline using different antigen-presenting cell types demonstrates that factors other than major histocompatibility complex class II density or tissue derivation of the antigen-presenting cell play a role in the activation of T cells in vitro. Finally, we demonstrate that in vitro generated hapten-specific T helper cell lines may not show strict major histocompatibility complex restriction.