Sempowski G D, Hale L P, Sundy J S, Massey J M, Koup R A, Douek D C, Patel D D, Haynes B F
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
J Immunol. 2000 Feb 15;164(4):2180-7. doi: 10.4049/jimmunol.164.4.2180.
The roles that thymus cytokines might play in regulating thymic atrophy are not known. Reversing thymic atrophy is important for immune reconstitution in adults. We have studied cytokine mRNA steady-state levels in 45 normal human (aged 3 days to 78 years) and 34 myasthenia gravis thymuses (aged 4 to 75 years) during aging, and correlated cytokine mRNA levels with thymic signal joint (sj) TCR delta excision circle (TREC) levels, a molecular marker for active thymopoiesis. LIF, oncostatin M (OSM), IL-6, M-CSF, and stem cell factor (SCF) mRNA were elevated in normal and myasthenia gravis-aged thymuses, and correlated with decreased levels of thymopoiesis, as determined by either decreased keratin-positive thymic epithelial space or decreased thymic sjTRECs. IL-7 is a key cytokine required during the early stages of thymocyte development. Interestingly, IL-7 mRNA expression did not fall with aging in either normal or myasthenia gravis thymuses. In vivo administration of LIF, OSM, IL-6, or SCF, but not M-CSF, i.p. to mice over 3 days induced thymic atrophy with loss of CD4+, CD8+ cortical thymocytes. Taken together, these data suggest a role for thymic cytokines in the process of thymic atrophy.
胸腺细胞因子在调节胸腺萎缩过程中可能发挥的作用尚不清楚。逆转胸腺萎缩对成人的免疫重建至关重要。我们研究了45例正常人类（年龄从3天至78岁）和34例重症肌无力患者的胸腺（年龄从4至75岁）在衰老过程中细胞因子mRNA的稳态水平，并将细胞因子mRNA水平与胸腺信号接头（sj）TCRδ切除环（TREC）水平相关联，TREC是活跃胸腺生成的分子标志物。白血病抑制因子（LIF）、制瘤素M（OSM）、白细胞介素-6（IL-6）、巨噬细胞集落刺激因子（M-CSF）和干细胞因子（SCF）的mRNA在正常和重症肌无力患者衰老的胸腺中升高，并且与胸腺生成水平降低相关，这通过角蛋白阳性胸腺上皮空间减少或胸腺sjTREC减少来确定。IL-7是胸腺细胞发育早期所需的关键细胞因子。有趣的是，在正常或重症肌无力患者的胸腺中，IL-7 mRNA表达并未随衰老而下降。对小鼠腹腔内连续3天注射LIF、OSM、IL-6或SCF（而非M-CSF）可诱导胸腺萎缩，伴有CD4+、CD8+皮质胸腺细胞丢失。综上所述，这些数据表明胸腺细胞因子在胸腺萎缩过程中发挥作用。
