Clearance Distinguish Th1 and Th2 Lymphocytes

In Th1 and Th2 lymphocytes, activation begins with identical stimuli but results in the production of different cytokines. The expression of some cytokine genes is differentially induced according to the amplitude and pattern of Ca signaling. Using fura2 Ca imaging of murine Th1 and Th2 clones, we observed that the Ca rise elicited following store depletion with thapsigargin is significantly lower in Th2 cells than in Th1 cells. Maximal Ca influx rates and whole-cell Ca currents showed that both Th1 and Th2 cells express indistinguishable Ca-release-activated Ca channels. Therefore, we investigated other mechanisms controlling the concentration of intracellular Ca, including K channels and Ca clearance from the cytosol. Whole-cell recording demonstrated that there is no distinction in the amplitudes of voltage-gated K currents in the two cell types. Caactivated K (KCa) currents, however, were significantly smaller in Th2 cells than in Th1 cells. Pharmacological equalization of Ca-activated K currents in the two cell types reduced but did not completely eliminate the difference between Th1 and Th2 Ca responses, suggesting divergence in an additional Ca regulatory mechanism. Therefore, we analyzed Ca clearance from the cytosol of both cell types and found that Th2 cells extrude Ca more quickly than Th1 cells. The combination of a faster Ca clearance mechanism and smaller Ca-activated K currents in Th2 cells accounts for the lower Ca response of Th2 cells compared with Th1 cells. The Journal of Immunology, 2000, 164: 1153–1160.