Or R, Renz H, Terada N, Gelfand E W
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado.
Clin Immunol Immunopathol. 1992 Sep;64(3):210-7. doi: 10.1016/0090-1229(92)90202-y.
The role of IL-4 and IL-2 on normal human T-cell activation and proliferation was studied. Both IL-2 and IL-4 were unable to induce proliferation of resting T cells. Therefore, we investigated their effect and the regulation of the T-cell proliferative response in competent T cells. T cells were rendered competent following incubation with PDB/ionomycin for 30 min or suboptimal concentrations of PHA for 60 min. Cells were then washed and recultured with PDB, IL-2, or IL-4 in the second or progression phase of the culture. Cells cultured in medium alone in this phase did not proliferate. IL-2 and IL-4 independently promoted competent T cells to proliferate to a similar degree as the response to PDB and the combination of IL-2 and IL-4 was not additive. The induction of competence and subsequent responsiveness to IL-2 and IL-4 could be maintained for about 24 hr after which time they become gradually less responsive to the interleukin in the progression phase. Addition of anti-IL-2R mAb or anti-IL-2 mAb resulted in selective inhibition of IL-2-mediated proliferation only. Similarly, addition of anti-IL-4 mAb resulted only in inhibition of IL-4-mediated proliferation. Addition of IL-2 during the progression phase led to an enhancement of IL-2R (TAC) expression while IL-4 did not affect IL-2R expression. The production of IL-2 and IL-4 by competent T cells could not be enhanced by the noncorresponding lymphokine. These results on the protein level were confirmed at the mRNA level as well and demonstrated that only PDB and IL-2 could induce IL-2 mRNA and PDB and IL-4 enhanced IL-4 mRNA. The immunosuppressive drug, cyclosporin A, failed to inhibit progression triggered by PDB, IL-2 or IL-4 in competent T cells. These findings suggest that IL-2 and IL-4 trigger T-cell proliferation through symmetrical, but independent pathways.
研究了白细胞介素-4（IL-4）和白细胞介素-2（IL-2）对正常人T细胞活化和增殖的作用。IL-2和IL-4均不能诱导静息T细胞增殖。因此，我们研究了它们在有反应能力的T细胞中的作用以及对T细胞增殖反应的调节。用佛波酯/离子霉素孵育30分钟或用亚最佳浓度的植物血凝素（PHA）孵育60分钟后，T细胞变得有反应能力。然后洗涤细胞，并在培养的第二阶段或进展阶段用佛波酯、IL-2或IL-4重新培养。在此阶段单独在培养基中培养的细胞不增殖。IL-2和IL-4独立地促进有反应能力的T细胞增殖，增殖程度与对佛波酯的反应相似，且IL-2和IL-4的联合作用无相加效应。在诱导有反应能力后，对IL-2和IL-4的后续反应性可维持约24小时，此后在进展阶段它们对白细胞介素的反应性逐渐降低。添加抗IL-2受体单克隆抗体（mAb）或抗IL-2 mAb仅导致对IL-2介导的增殖的选择性抑制。同样，添加抗IL-4 mAb仅导致对IL-4介导的增殖的抑制。在进展阶段添加IL-2导致IL-2受体（TAC）表达增强，而IL-4不影响IL-2受体表达。有反应能力的T细胞产生IL-2和IL-4的能力不会被不相应的淋巴因子增强。这些在蛋白质水平上的结果在mRNA水平上也得到了证实，表明只有佛波酯和IL-2能诱导IL-2 mRNA，佛波酯和IL-4能增强IL-4 mRNA。免疫抑制药物环孢素A未能抑制有反应能力的T细胞中由佛波酯、IL-2或IL-4触发的进展。这些发现表明，IL-2和IL-4通过对称但独立的途径触发T细胞增殖。
