Dobber R, Hertogh-Huijbregts A, Rozing J, Bottomly K, Nagelkerken L
Section of Immunology, Institute of Ageing and Vascular Research TNO, Leiden, The Netherlands.
Dev Immunol. 1992;2(2):141-50. doi: 10.1155/1992/57057.
It is well known that immune reactivity declines with age. Recently, we demonstrated that the age-related decrease in IL-2 production by CD4+ T cells was accompanied by an increased production of IL-4 and interferon-gamma (IFN-gamma). This age-related shift in the profile of lymphokine production was related to phenotypic changes within the CD4+ T-cell subset, that is, a decrease in the percentage of CD45RB++ CD4+ T cells and an increase in the percentage of Pgp-1+ CD4+ T cells. To study whether these age-related changes were due to previous antigenic exposure, we performed a phenotypic and functional analysis on splenic CD4+ T cells isolated from individual germ-free (GF), specific pathogen-free (SPF), and clean conventional (CC) mice. Interestingly, the total number of splenic CD4+ T cells in GF mice was twofold lower as compared to age-matched SPF or CC mice, regardless whether mice were analyzed at young (10 weeks) or at advanced age (13-14 months). Unexpectedly, the phenotypic composition of the CD4+ T-cell subset was comparable in the GF, SPF, and CC mice as determined by the expression of CD45RB and Pgp-1, indicating that CD4+ T cells with a naive phenotype (CD45RB++ Pgp-1-) were not enriched in GF mice. Moreover, at an age of 13-14 months, CD4+ T cells from GF mice frequently produced more IL-4 and IFN-gamma than their CC counterparts. These lymphokine data showed, therefore, that a relatively high proportion of CD4+ T cells with a memory phenotype can also be defined in GF mice on the basis of their function. The contamination of GF mice with a colonization resistant factor (CRF flora) resulted in twofold higher numbers of splenic CD4+ T cells. Surprisingly, not only CD4+ T cells with a memory phenotype (CD45RB-/+ Pgp-1++) had expanded, but also CD4+ T cells with a naive (CD45RB++ Pgp-1-) phenotype. Our results, therefore, strongly suggest that the expansion of naive CD4+ T cells in the periphery is mediated by the intestinal microflora.
众所周知，免疫反应性会随着年龄的增长而下降。最近，我们证明，CD4 + T细胞产生白细胞介素-2（IL-2）的量随年龄增长而减少的同时，白细胞介素-4（IL-4）和干扰素-γ（IFN-γ）的产生量却增加了。这种与年龄相关的淋巴因子产生谱的变化与CD4 + T细胞亚群内的表型变化有关，即CD45RB++ CD4 + T细胞百分比的降低和Pgp-1 + CD4 + T细胞百分比的增加。为了研究这些与年龄相关的变化是否是由于先前的抗原暴露所致，我们对从无菌（GF）、无特定病原体（SPF）和清洁常规（CC）小鼠个体中分离出的脾脏CD4 + T细胞进行了表型和功能分析。有趣的是，与年龄匹配的SPF或CC小鼠相比，GF小鼠脾脏CD4 + T细胞的总数要低两倍，无论小鼠是在年轻时（10周）还是在老年时（13 - 14个月）进行分析。出乎意料的是，通过CD45RB和Pgp-1的表达确定，GF、SPF和CC小鼠中CD4 + T细胞亚群的表型组成是可比的，这表明具有幼稚表型（CD45RB++ Pgp-1-）的CD4 + T细胞在GF小鼠中并未富集。此外，在13 - 14个月大时，GF小鼠的CD4 + T细胞比其CC对应物更频繁地产生更多的IL-4和IFN-γ。因此，这些淋巴因子数据表明，基于其功能，在GF小鼠中也可以定义相对较高比例的具有记忆表型的CD4 + T细胞。用定植抗性因子（CRF菌群）污染GF小鼠导致脾脏CD4 + T细胞数量增加两倍。令人惊讶的是，不仅具有记忆表型（CD45RB-/+ Pgp-1++）的CD4 + T细胞有所扩增，而且具有幼稚（CD45RB++ Pgp-1-）表型的CD4 + T细胞也有所扩增。因此，我们的结果强烈表明，外周幼稚CD4 + T细胞的扩增是由肠道微生物群介导的。
