Nishimura H, Hattori S, Ueda G, Abe M, Yang K, Nozawa S, Okamoto H, Zhang D, Tsurui H, Hirose S
Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan.
Int Immunol. 1995 Jul;7(7):1115-23. doi: 10.1093/intimm/7.7.1115.
Using two mAb, one specific to the alternative exon 6-dependent epitope of CD45 molecules (JH6.2) and one a natural thymocytotoxic autoantibody (NTA) with an unknown reactive epitope (NTA260), we subdivided splenic CD4+ T cells from 2-month-old BALB/c mice into five phenotypically distinct subsets. CD45RC+NTA260- (S I) cells were phenotypically analogous to CD4+ T cells predominating in newborn mice and produced a significant amount of IL-2, but not so IL-4, IL-10 or IFN-gamma when stimulated with immobilized anti-CD3 mAb in vitro. They appeared to consist mainly of naive ThP cells. The CD45RC+NTA260+ (S II) subset also produced IL-2, but not other cytokines; however, the IL-2 levels produced were much higher than seen with the S I subset, thereby suggesting the predominance of further maturated ThP cells. The CD45RC-NTA260+ (S III) subset mainly produced IL-4, IL-10, IFN-gamma and less IL-2, and contained memory cells that helped the secondary antibody response to a recall antigen, and hence contained Th2 and probably a mixture of Th0 and Th1 cells. The CD45RC-NTA260- (S IV) subset was a poor responder to the immobilized anti-CD3 mAb. The CD45RCbrightNTA260dull (S V) subset consisted of a small number of cells that were phenotypically analogous to activated CD4+ T cells. While an age-associated decrease in the proportion of S I and less markedly in S II and in turn increase in S III subsets of CD4+ T cells occurred in normal BALB/c mice, autoimmune disease-prone (NZB x NZW)F1 mice showed a marked age-associated decrease in the proportion of not only S I, II but also III subsets. As aged (NZB x NZW)F1 mice carry CD4+ T helper cells for IgG anti-DNA antibody production, such age-associated polarization to the S IV subset appears to be critical in the pathogenesis of autoimmune disease in these mice.
我们使用两种单克隆抗体（mAb），一种特异性针对CD45分子的可变外显子6依赖性表位（JH6.2），另一种是具有未知反应表位的天然胸腺细胞毒性自身抗体（NTA，即NTA260），将2月龄BALB/c小鼠的脾脏CD4⁺ T细胞细分为五个表型不同的亚群。CD45RC⁺NTA260⁻（SI）细胞在表型上类似于新生小鼠中占主导的CD4⁺ T细胞，体外经固定化抗CD3单克隆抗体刺激后可产生大量白细胞介素-2（IL-2），但不产生IL-4、IL-10或γ干扰素（IFN-γ）。它们似乎主要由幼稚ThP细胞组成。CD45RC⁺NTA260⁺（SII）亚群也产生IL-2，但不产生其他细胞因子；然而，其产生的IL-2水平远高于SI亚群，这表明存在更多成熟的ThP细胞。CD45RC⁻NTA260⁺（SIII）亚群主要产生IL-4、IL-10、IFN-γ，产生的IL-2较少，并且包含有助于对回忆抗原产生二次抗体应答的记忆细胞，因此包含Th2细胞以及可能的Th0和Th1细胞的混合物。CD45RC⁻NTA260⁻（SIV）亚群对固定化抗CD3单克隆抗体反应较差。CD45RCbrightNTA260dull（SV）亚群由少量表型类似于活化CD4⁺ T细胞的细胞组成。在正常BALB/c小鼠中，CD4⁺ T细胞的SI亚群比例随年龄增长而下降，SII亚群下降不太明显，SIII亚群比例相应增加，而自身免疫病易感的（NZB×NZW）F1小鼠不仅SI、II亚群比例随年龄增长显著下降，III亚群比例也显著下降。由于衰老的（NZB×NZW）F1小鼠携带产生IgG抗DNA抗体的CD4⁺辅助性T细胞，这种与年龄相关的向SIV亚群的极化似乎在这些小鼠自身免疫病的发病机制中起关键作用。
