Abnormal polarization of CD4^+ T cell subsets in autoimmune-Prone New Zealand mice.

自身免疫易感性新西兰小鼠CD4^+ T细胞亚群的异常极化。系统性红斑狼疮（SLE）患者血液中携带活化抗原（如HLA-DR和-DP）的CD4^+ T细胞的高频率表明，在这种疾病条件下，自身反应性CD4^+ T细胞持续活化。在本研究中，我们使用两种不同的早期T细胞激活标记CD69和NTA204分析了sled易发性NZB和（NZB*NZW） F1小鼠脾脏中自发激活的CD4^+ T细胞。在NZB和（NZB*NZW） F1中观察到CD69^+和NTA204^+活化的CD4^+ T细胞的比例明显与年龄相关，但在非自身免疫性NZW和BALB/c小鼠中没有。有趣的是，有三种不同的活化T细胞；一个单独使用CD69，一个使用NTA204，一个同时使用CD69和NTA204。对T细胞受体（TCR） V β库的研究表明，这些活化的T细胞没有扭曲的TCR V β库使用。小鼠CD4^+ T细胞可细分为4个不同的亚群，CD62L （l -选择素）和NTA260（一种由自身免疫性NZB小鼠的杂交瘤单克隆自身抗体定义的抗原）阳性或阴性。结果发现，所有三种活化的CD4^+ T细胞亚群都包含在CD62L-NTA260-CD4^+ T细胞亚群中。这个亚群是独特的，因为它既不属于幼稚的也不属于记忆的CD4^+ T细胞。根据其细胞因子产生模式，它也不像Th1或Th2一样起作用。由于CD62L-NTA260-CD4^+ T细胞亚群成为老年NZB和（NZB*NZW） F1小鼠CD4^+ T细胞的主要群体，对该亚群的进一步表型和功能分析可能有助于深入了解SLE发病机制中自身反应性T细胞的产生机制。

Abnormal polarization of CD4^+ T cell subsets in autoimmune-Prone New Zealand mice.High frequencies of CD4^+ T cells bearing activation antigens such as HLA-DR and -DP in blood of patients with systemic lupus erythematosus (SLE) suggest that a continuous activation of autoreactive CD4^+ T cells occurs in this disease condition. In the present stidies, we analyzed spontaneously activated CD4^+ T cells in spleens of SLE-Prone NZB and (NZB*NZW) F1 mice, using two distinct early T cell activation markers, CD69 and NTA204. A marked age-associated increase in the proportion of each CD69^+ and NTA204^+ activated CD4^+ T cells was observed in NZB and (NZB*NZW) F1, but not in non-autoimmune NZW and BALB/c mice. Interestingly, there were phenotypically separate, three types of activated T cells ; one with CD69 alone, one with NTA204, and one with both CD69 and NTA204, Studies of T cell receptor (TCR) V bata repertoire showed that these activated T cells had no skewed TCR V beta repertoire usages. Murine CD4^+ T cells could be subdivided into 4 distinct subsets, either positive or negative for CD62L (L-selectin) and NTA260, an antigendefined by a hybridoma monoclonal autoantibody from autoimmune NZB mice. It was found that all three activated CD4^+ T cell subpopulations were included in the CD62L-NTA260-CD4^+ T cell subset. This subset was unique because it belonged to neither naive nor memory CD4^+ T cells. It also did not functioon as either Th1 or Th2, based on its cytokine production patterns. As such CD62L-NTA260-CD4^+ T cell subset became the major population of CD4^+ T cells in aged NZB and (NZB*NZW) F1 mice, further phenotypical and functional analysis of this subset may provide insightsinto the mechanisms of the generation of autoreactive T cells responsible for the pathogenesis of SLE.