Kosugi A, Shearer G M
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
J Immunol. 1991 Mar 1;146(5):1416-21.
The effects of cyclosporin A (CsA) on the generation of NK cells were studied using syngeneic bone marrow transplanted mice subsequently treated with CsA (BMT/CsA mice). In contrast to a severe reduction in T cells that was reported previously, these mice exhibited a marked enhancement of splenic NK activity. The enhanced NK activity was mediated by NK1.1+, Thy-1- cells as assessed by antibody plus complement treatment, and was concomitant with an absolute increase in the numbers of NK1.1+ cells as assessed by flow cytometry. Because the depletion of host-derived, mature NK cells by injection of anti-asialo GM1 antibody before bone marrow reconstitution did not affect the enhancement of NK activity, CsA appeared to augment the generation of NK cells from bone marrow precursors. To investigate a possible relationship between the enhancement of NK activity and the maturational arrest of T cells in the thymus induced by CsA, mice were thymectomized, followed by irradiation, bone marrow reconstitution, and CsA treatment. These mice exhibited as strong enhancement of splenic NK activity as BMT/CsA mice, suggesting that the CsA-induced effect on NK cells is distinct from its effect on T cell development in the thymus. Taken together, these results are the first demonstration of the positive effect of CsA on NK cell generation and may be of importance in clinical bone marrow transplantation.
使用同基因骨髓移植小鼠（随后用环孢素A（CsA）处理，即BMT/CsA小鼠）研究了环孢素A（CsA）对自然杀伤细胞（NK细胞）生成的影响。与先前报道的T细胞严重减少相反，这些小鼠脾脏NK活性显著增强。通过抗体加补体处理评估，增强的NK活性由NK1.1⁺、Thy-1⁻细胞介导，并且通过流式细胞术评估，伴随着NK1.1⁺细胞数量的绝对增加。由于在骨髓重建前注射抗唾液酸GM1抗体耗尽宿主来源的成熟NK细胞并不影响NK活性的增强，CsA似乎增强了骨髓前体细胞产生NK细胞的能力。为了研究NK活性增强与CsA诱导的胸腺中T细胞成熟停滞之间的可能关系，对小鼠进行胸腺切除，随后进行照射、骨髓重建和CsA处理。这些小鼠脾脏NK活性增强程度与BMT/CsA小鼠一样强，表明CsA对NK细胞的诱导作用与其对胸腺中T细胞发育的作用不同。综上所述，这些结果首次证明了CsA对NK细胞生成具有积极作用，并且可能在临床骨髓移植中具有重要意义。
