Multiparameter Evaluation Of Mechanism Of AIDS Immune Nonresponser (INRs)

[Objective]:Our study aims to analyse the characteristics of the immune reconstitution of HIV/AIDS patients after HAART and the pathogenesis of immune non-response.[Methods]:Erollment began in 2003. All 55 adult patients coming from HIV/AIDS research center of Peking Union Medical Collage Hospital (PUMCH) were followed in an identical manner at the out-patient department. They were followed from baseline to month 36(M36). T cell subset and plasma viral load will done in baseline, Ml, M3, M6, M9, M12, M18, M24, M30, M36. Lymphcyte subsets include B cell count (CD 19+), NK cell count (CD16+CD56+), CD4 and CD8+T cell count(CD3+CD4+, CD3+CD8+), naive CD4+T cell count(CD4+CD45RA+CD62L+), memory CD4+T cell count(CD4+CD45RA-), the percentage of CD8+T cell actived subset(CD8+CD38+/CD8+, CD8+HLA-DR+/CD8+). PBMCs were isolated and cryopreserved. If the treated patient's plasma viral load was undetectable for over 1 year, the subject would be further divided into immune response group (IR) (n=15) or immune non-response group (INR) (n=11). The PBMC of baseline,6M,12M,24M, 36M were thawed for FCM analysis. The FCM analysis included the percentage of CD4+T cell actived subset(CD8+CD38+/CD8+, CD8+HLA-DR+/CD8+), the recent thymic emigrants of CD4+T cell percentage (CD4+CD45RA+CD31+/CD4+), the early apoptosis CD4+T cell percentage (CD4+Annexin V+PI-/CD4+), the CD4+regulatory T cell percentage (CD4+CD25+FoxP3+/CD4+), and the differentiation subset of CD4+memory cells expression of CCR7 and CD27.[Results]:1. At baseline, the mean CD4+T cell count was 37±36/ul in INR group which was significantly higher than the mean CD4+T cell count of IR group (172±87/ul) (P < 0.01). The recent thymic emigrants of CD4+T cell percentage was 11.9±7.0% in IR group, which was significantly higher than those of INR group(P=0.023). The early apoptosis CD4+T cell percentage was 4.1±3.3% in IR group which was significantly lower than those of INR group(P< 0.01). The CD4+regulatory T cell percentage was 6.9±3.5% in INR group, much higher than that of IR goup(P<0.01).2. NK cell count, B cell count was increased after HAART in both groups. This increase was more significant in the early phase of treatment. The increase of the mean B cell count was more significant in INR group than in IR gorup.3. After 36-month-treatment, the increase of memory CD4+T cell count was 128±61/ul in IR group and 118±67/ul in INR group; the increase of naive CD4+T cell count was 107±82/ul in IR group and 46±18/ul in INR group(P< 0.01). The difference of CD4+T cell count after HAART was mainly occurred in naive CD4+T cells.4. The percentages of CD8+T cell actived subsets were similar in both AIDS patients groups in baseline. But after threatment, the pesentage of CD8+CD38+/CD8+ decreased more rapidly in IR group than in INR group.5. After 6-month-treatment, the early differentiation subset of memory CD4+T cell (CD4+CD45RA-CCR7+CD27+/CD4+CD45RA-) was much higher in IR group than in INR group.6. The percentage of early apoptosis CD4+T cell subset was positively corelated with the percentage of both CD8+T cell actived subsets(CD8+CD38+, r=0.225, p=0.016; CD8+HLA-DR+, r=0.229, p=0.014); The percentage of early apoptosis CD4+T cell subset was positively corelated with the CD4+regulatory T cell percentage (r=0.205, p=0.029).[Conclusions]:1. After HAART, CD4+T cell was increased rapidly in the early phase. This early phase increase reflected the memory CD4+T cell redistribution. After the early phase, the second phase increase reflected the slow and significant increase of the naive CD4+T cell count. After 36-month-treatment, the discrepancy of CD4+T cell count increase of the two groups was mainly occurred in naive CD4+T cell subset. The increase of NK cell count was similar in both groups. The increase of B cell count was more significant in INR group than in IR group.2. The lower baseline CD4+T cell count, the lower percentage of recent thymic emigrants CD4+T cell, the higher early apoptosis CD4+T cell percentage, the higher CD4+regulatory T cell percentage were the presentiment of immune non-response. After treatment, the slower decrease of CD8+CD38+activated subset of CD8+T cell was also indicate the immune non-response.3. The percentage of active subset of CD8+T cell was positively correlated with the early apoptosis CD4+T cell percentage. The CD4+regulatory T cell percentage was positively correlated with the early apoptosis CD4+T cell percentage.