Pantel K, Nakeff A
Wayne State University School of Medicine, Department of Internal Medicine, Detroit, MI 48201.
Exp Hematol. 1990 Sep;18(8):863-7.
We have examined the importance of L3T4+ (murine equivalent to CD4+) cells for hematopoietic regulation in vivo in unperturbed mice and mice recovering from total-body irradiation (TBI) using a cytotoxic monoclonal antibody (MoAb) raised with the GK 1.5 hybridoma. Ablating L3T4+ cells in "normal" (unperturbed) B6D2F1 mice substantially decreased the S-phase fraction (determined by in vivo hydroxyurea suicide) of erythroid progenitor cells (erythroid colony-forming units, CFU-E) as compared to the pretreatment level (10% +/- 14.1% [day 3 following depletion] vs 79.8% +/- 15.9%, respectively) with a corresponding decrease in the marrow content of CFU-E at this time to approximately 1% of the pretreatment value. Although the S-phase fraction of CFU-GM was decreased to 2.2% +/- 3.1% 3 days after L3T4+ cell ablation from the 21.3% +/- 8.3% pretreatment value, CFU-GM cellularity showed little change over the 3 days following anti-L3T4 treatment. Anti-L3T4 MoAb treatment had little or no effect on either the S-phase fraction or the marrow content of hematopoietic "stem cells" (spleen colony-forming units, CFU-S) committed to myeloerythroid differentiation. Ablating L3T4+ cells prior to a single dose of 2 Gy TBI resulted in significantly reduced marrow contents of CFU-S on day 3 and granulocyte-macrophage colony-forming units (CFU-GM) on day 6 following TBI, with little or no effect on the corresponding recovery of CFU-E. The present findings provide the first in vivo evidence that L3T4+ cells are involved in: 1) maintaining the proliferative activity of CFU-E and CFU-GM in unperturbed mice and 2) supporting the restoration of CFU-S and CFU-GM following TBI-induced myelosuppression.
我们使用由GK 1.5杂交瘤产生的细胞毒性单克隆抗体（MoAb），研究了L3T4 +（相当于小鼠CD4 +）细胞在未受干扰的小鼠和从全身照射（TBI）恢复的小鼠体内对造血调节的重要性。与预处理水平相比，在“正常”（未受干扰）的B6D2F1小鼠中消除L3T4 +细胞，显著降低了红系祖细胞（红系集落形成单位，CFU-E）的S期分数（通过体内羟基脲自杀法测定）（分别为[耗竭后第3天] 10%±14.1% vs 79.8%±15.9%），此时CFU-E的骨髓含量相应降低至预处理值的约1%。虽然在L3T4 +细胞消融后3天，CFU-GM的S期分数从预处理值21.3%±8.3%降至2.2%±3.1%，但在抗L3T4治疗后的3天内，CFU-GM细胞数量变化不大。抗L3T4 MoAb治疗对致力于髓红系分化的造血“干细胞”（脾集落形成单位，CFU-S）的S期分数或骨髓含量几乎没有影响。在单次2 Gy TBI之前消除L3T4 +细胞，导致TBI后第3天CFU-S的骨髓含量显著降低，第6天粒细胞-巨噬细胞集落形成单位（CFU-GM）显著降低，而对CFU-E的相应恢复几乎没有影响。本研究结果首次提供了体内证据，表明L3T4 +细胞参与：1）维持未受干扰小鼠中CFU-E和CFU-GM的增殖活性，以及2）支持TBI诱导的骨髓抑制后CFU-S和CFU-GM的恢复。
