In vivo significance of T-reg cells during FIV infection

FIV 感染期间 T-reg 细胞的体内意义

• 批准号: 7005510
• 负责人: Gregg A Dean
• 金额: $ 29.2万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-15 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7005510
• 关键词: HIV infections; Retroviridae disease; T lymphocyte; apoptosis; cats; cell cell interaction; disease /disorder model; feline immunodeficiency virus; immune response; immunopathology; immunoregulation; pathologic process

DESCRIPTION (provided by applicant): We have described CD4+CD25+ Treg cells in the cat and demonstrated that they are chronically activated in feline immunodeficiency virus (FIV) infected animals. Treg cells from FIV-infected cats significantly inhibited proliferation of CD4+CD25- T cells, and are apparently activated in vivo as a result of the chronic FIV infection. As activated Treg cells are non-antigen specific in their suppressive function, it is possible that these cells could in turn suppress or anergize CD4+ T helper responses to a variety of antigens including FIV antigen and thereby contribute to the acquired immunodeficiency syndrome (AIDS) characteristic of this infection. The same observation has recently been reported in HIV-1 infected people and interestingly, increased levels of Treg function were associated with a favorable clinical status or respose to HAART. Normally, Treg function is critical to limit and down-regulate immune responses, preventing excessive inflammation and autoimmune disease. Whether Treg cells in HIV infection are beneficial or detrimental is unclear and the answer may depend on the stage of disease. It is possible that HIV-induced Treg activity during acute infection may limit the scope and efficacy of the anti-viral response, whereas Treg activity during asymptomatic infection may serve to control chronic immune activation and limit availability of activated target cells. The most definitive way to address the significance of Treg function during HIV infection is to deplete Treg cells in an animal model. In these studies we will employ the FIV/cat model of HIV to: 1.) Determine whether depletion of Treg cells before or immediately after FIV infection results in a more effective anti-viral immune response, and 2.) Determine whether depletion of Treg cells during the asymptomatic phase of FIV infection results in the expansion of antiviral T-cell immunity and/or change in plasma viremia. Results from these studies will provide a clinical understanding of Treg function in HIV infection and will guide future approaches to modulate Treg function.

描述（由申请人提供）：我们描述了猫中的CD 4 + CD 25 + Treg细胞，并证明它们在猫免疫缺陷病毒（FIV）感染的动物中被慢性激活。来自FIV感染猫的Treg细胞显著抑制CD 4 + CD 25- T细胞的增殖，并且由于慢性FIV感染而在体内明显活化。由于活化的Treg细胞在其抑制功能中是非抗原特异性的，因此这些细胞可能进而抑制或无能化CD 4 + T辅助细胞对包括FIV抗原在内的多种抗原的应答，从而促成该感染的获得性免疫缺陷综合征（AIDS）特征。最近在HIV-1感染者中报道了相同的观察结果，有趣的是，Treg功能水平的增加与良好的临床状态或对HAART的反应相关。通常，Treg功能对于限制和下调免疫反应，预防过度炎症和自身免疫性疾病至关重要。HIV感染中的Treg细胞是有益的还是有害的尚不清楚，答案可能取决于疾病的阶段。在急性感染期间HIV诱导的Treg活性可能限制抗病毒应答的范围和功效，而在无症状感染期间Treg活性可能用于控制慢性免疫活化并限制活化的靶细胞的可用性。解决HIV感染期间Treg功能的重要性的最确定的方法是耗尽动物模型中的Treg细胞。在这些研究中，我们将采用HIV的FIV/cat模型：1.确定在FIV感染之前或之后立即耗尽Treg细胞是否导致更有效的抗病毒免疫应答，和2.）确定在FIV感染的无症状阶段Treg细胞的耗竭是否导致抗病毒T细胞免疫的扩增和/或血浆病毒血症的变化。这些研究的结果将提供对HIV感染中Treg功能的临床理解，并将指导未来调节Treg功能的方法。