Sleasman J W, Morimoto C, Schlossman S F, Tedder T F
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
Eur J Immunol. 1990 Jun;20(6):1357-66. doi: 10.1002/eji.1830200623.
Human helper T lymphocytes can be dissected into two functionally distinct subpopulations based on expression of the CD45RA (2H4) or CD45R0 (UCHL-1) surface antigens. While both subpopulations are able to induce equivalent levels of B cell activation and proliferation, only the CD4+CD45RA- subpopulation is capable of inducing B cell differentiation in pokeweed mitogen (PWM)-stimulated cultures. To define the mechanism responsible for the dichotomy between induction of proliferation and differentiation by the two CD4+ subpopulations, we examined the abilities of the purified T cell subpopulations to produce lymphokine mRNA following T cell activation. Northern analysis revealed that both subpopulations produced interleukin (IL) 2 and interferon (IFN)-gamma mRNA following PWM activation. The CD4+CD45RA- subpopulation, however, produced higher levels of IFN-gamma mRNA and the CD4+CD45RA+ cells produced higher levels of IL 2 mRNA. Neither subpopulation elaborated detectable mRNA for IL 4, IL 5 or IL 6. Of greatest significance was that the addition of recombinant or T cell-derived lymphokines could not compensate for the inability of the CD4+CD45RA+ subpopulation to induce B cell differentiation in PWM assays. Direct T-B cell contact was required for the optimal induction B cell differentiation in these assays, suggesting that CD4+CD45RA+ T cells were deficient in their ability to directly deliver the T cell-B cell signals required for B cell differentiation. These results suggest that the differential ability of the two subpopulations of CD4+ T cells to induce B cell differentiation does not result from differences in lymphokines elaborated, but may result from differences in their abilities to interact directly with B cells to initiate differentiation.
人类辅助性T淋巴细胞可根据CD45RA（2H4）或CD45R0（UCHL-1）表面抗原的表达分为两个功能不同的亚群。虽然这两个亚群都能够诱导同等水平的B细胞活化和增殖，但只有CD4+CD45RA-亚群能够在商陆有丝分裂原（PWM）刺激的培养物中诱导B细胞分化。为了确定两个CD4+亚群在诱导增殖和分化方面存在差异的机制，我们检测了纯化的T细胞亚群在T细胞活化后产生淋巴因子mRNA的能力。Northern分析显示，两个亚群在PWM激活后均产生白细胞介素（IL）2和干扰素（IFN）-γ mRNA。然而，CD4+CD45RA-亚群产生更高水平的IFN-γ mRNA，而CD4+CD45RA+细胞产生更高水平的IL 2 mRNA。两个亚群均未产生可检测到的IL 4、IL 5或IL 6 mRNA。最重要的是，在PWM试验中，添加重组或T细胞来源的淋巴因子并不能弥补CD4+CD45RA+亚群诱导B细胞分化能力的不足。在这些试验中，最佳诱导B细胞分化需要T-B细胞直接接触，这表明CD4+CD45RA+ T细胞在直接传递B细胞分化所需的T细胞-B细胞信号方面存在缺陷。这些结果表明，两个CD4+ T细胞亚群诱导B细胞分化的能力差异并非源于所分泌淋巴因子的不同，而是可能源于它们与B细胞直接相互作用以启动分化的能力差异。
