Pathogenic Mechanisms In HIV Disease

HIV感染者免疫系统的特点是辅助性/诱导性T淋巴细胞数量减少。研究表明，间歇性输注T细胞衍生的细胞因子IL-2可以导致CD4+池大小的显著增加。负责这种增加的细胞的特征是CD25分子的表达，这是最近描述的CD4+T细胞的T调节亚群的特征。对IL-2治疗环境中的CD4+CD25+细胞的详细分析表明，它们是外周扩张的产物，而不是胸腺产生新细胞的结果。他们被发现代表了一个不同的细胞家族，能够识别广泛的抗原。这些细胞与T调节细胞相似，因为它们表达转录因子Foxp3的水平增加，但与这些细胞的不同之处在于，它们具有幼稚细胞和记忆细胞的表型特征，只有微弱的抑制活性。这些细胞因子扩增的细胞表现出较低的自发性细胞死亡率，这可能是导致CD4+T细胞池中周转率持续较低的原因。 在其他合作工作中，对测量IL-7受体(CD127)的阿尔法链的技术进行了优化，为这种淋巴细胞生长和存活因子的临床试验做准备。在延迟加工或冷冻的设置中注意到CD127水平的降低。

The immune systems of patients with HIV infection are characterized by a decrease in the number of helper/inducer (CD4) T lymphocytes. Studies have demonstrated that intermittent infusions of the T cell derived cytokine IL-2 can lead to profound increases in the size of the CD4+ pool. The cells responsible for this increase are characterized by expression of the CD25 molecule, a characteristic of the recently described T regulatory subset of CD4+ T cells. A detailed analysis of the CD4+CD25+ cells seen in the setting of IL-2 therapy revealed that they were the product of peripheral expansion, rather than the generation of new cells from the thymus. They were found to represent a diverse family of cells with the ability to recognize a wide array of antigens. These cells were similar to T regulatory cells in that they expressed increased levels of the transcription factor foxP3, however different from these cells in that they had phenotypic characteristics of both naive and memory cells and only weak suppressive activity. These cytokine-expanded cells exhibited low rates of spontaneous cell death and may be responsible for sustained low rates of turnover in the CD4+ T cell pool. In other collaborative work, techniques were optimized for the measurement of the alpha chain of the IL-7 receptor (CD127) in preparation for clinical trials of this lymphocyte growth and survival factor. Decreased levels of CD127 were noted in the setting of delayed processing or freezing.