The Dynamics Of T Helper 17 In The Peripheral Blood Of SHIV Infected Chinese Rhesus Macaques

AIDS(Acquired Immunodeficiency Syndrome), caused by Human Immunodeficiency Virus (HIV) infection, has become the leading fatal infectious disease threatening human health. One of the most significant symptoms in HIV infection is the great loss of CD4+ T lymphocytes. Classically, CD4+ T helper cell is divided into two subtypes: IFNy secreting T helper 1 cells and IL-4 secreting T helper 2 cells. As a newly demonstrated subpopulation of T helper cell, IL-17 and IL-22 secreting Th17 cells play a critical role in autoimmune disease, inflammation and infectious immunology. In this research, eight Chinese-origin rhesus macaques were inoculated intravenously with SHIV-sfl62p4 while the other four were exposed to 10 low-dose SHIV-sfl62p4 to construct stable SHIV infection. Intracellular cytokines staining and Flow Cytometry were used to evaluate the levels of different CD4+ T helper subpopulations and their balance pre-and-post infection. Besides, the correlation between these levels and viral load or the frequency of CD4+ T memory cells respectively, which have been associated with AIDS progression, were also analysed. Referring to sequences of nuclear transcriptional regulatory factors and cytokines which regulated the differentiation of these different CD4+ T cell subpopulations, primers and Taqman probes for real time RT-PCR assay were designed, the level and tendency of mRNA level of these factors pre and post infection were examined.According to our data, in acute phase of infection, the correlation between Th17 frequency and viral load was significant in i.v. challenge group; the ratio of IL-17+ cells over Foxp3+ cells, which decreased in the first few weeks and increased later, was negatively correlated to viral load, both in intravenously inoculated group and rectum exposed group. The ratio in intravenously inoculated group also has significant positive correlation to the frequency of CD4+ T memory cell. Besides, the ratio of RORyt and Foxp3 on transcriptional level is also correlated to viral load. CCR5-tropism SHIV have been extensively used in AIDS research, we are the first to use CCR5-tropism SHIV infected Chinese rhesus macaques to investigate the dynamics of both different CD4+ T helper subpopulations and their balance after SHIV infection. Besides, the correlations between these changes and disease progression were also elucidated. It provided important data for understanding the role and mechanism of Th17 in the acute phase of HIV infection...