Cells of Dictyostelium discoideum respond chemotactically to.cyclic AMP [l] and to folic acid [3]. Cyclic AMP is a most efficient attractant for cells of the aggregation phase [2], folic acid is more effective with preaggregation cells [4]. Both cyclic AMP and folic acid stimulate also cell development from the preaggregation phase to the aggregation competent state [S-8]. During this process the cells acquire the capacity to synthesize cyclic AMP periodically, and to release it into the extracellular space in form of pulses [9] . The administration of cyclic AMP or folic acid pulses accelerates the onset of sustained oscillations [5,8] .The cyclic-AMP induced responses are known to be mediated by cell-surface receptors [lo-121. The intermediate steps in signal processing from the receptors to the various intracellular targets are unknown. In the present communication we show that upon stimulation of early preaggregation cells with folic acid a rapid increase of the cyclic GMP concentration is induced. A biphasic increase of cyclic GMP is observed in late preaggregation cells stimulated by cyclic AMP. The second cyclic GMP peak is succeeded by a cyclic AMP peak known to be based on the activation of adenylate cyclase [ 131. Free-running oscillations of cyclic GMP were observed together with the periodic formation of cyclic AMP pulses, and the cyclic GMP peaks seemed to occur slightly in advance of the cyclic AMP peaks.

BALB/c nu/nu mice were grafted with embryonic 14-day-old C57BL/6 thymi which were transplanted either nontreated or after elimination of hemopoietic cells with 2-deoxyguanosine. In both types of grafts host cells developed normally into functional thymocytes. Thymocytes from 2-deoxyguanosine-treated but not from untreated grafts contained as many cytolytic T lymphocyte precursors specific for class I MHC antigens on thymus epithelium as normal BALB/c thymocytes. As cytolytic T lymphocyte precursors were neither suppressed nor activated in these grafts it is concluded that thymocytes ignore class I MHC antigens expressed on thymus epithelium.

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Folic acid is known to be a chemoattractant of pre-aggregation cells of Dictyostelium discoideum. When supplied in pulses, folic acid induces biochemical oscillations and stimulates the development of pre-aggregation to aggregation-competent amoebae. The continuous supply of folic acid has no stimulatory effect. Folic-acid-induced oscillations are accompanied by periodic changes in the cyclic AMP concentration. Pulses of folic acid applied with rhythms between 7 and 11 min efficiently induce oscillations. In contrast, a rhythm of 2 min neither induces oscillations nor suppresses them. Cells start to oscillate with a rhythm of about 8 min. This inherent rhythm is independent of the inducing rhythm. Oscillating cells are less sensitive to folic acid than pre-oscillating ones. They respond only to high concentrations of folic acid which also interact with the oscillating system.