T-Regulatory Cells Correlate with Persistent Human Immunodeficiency Virus Infection in Lymph Nodes.
Shanxiang Zhang, Julian Arce, Chih-Kang Huang, Qiulu Pan, Amy Fox, Momka Narlieva, Yungtai Lo, Howard Ratech. Albert Enstein College of Medicine, Bronx, NY; Montefiore Medical Center, Bronx, NY
Background: It is controversial whether T regulatory (Treg) cells in patients with human immunodeficiency virus (HIV) infection are beneficial by limiting immune activation or detrimental by inhibiting HIV-specific immune responses. Therefore, we investigated Tregs in lymph nodes (LN) in patients with early- and late-stages of HIV infection, with particular attention to plasma HIV viral load (VL) and LN HIV VL.
Design: RNA was extracted from paraffin-embedded, formalin-fixed LN biopsies from HIV+ patients and used to perform a quantitative reverse real-time PCR assay that was originally developed for measuring plasma HIV-1 VL (Abbott RealTime HIV-1 Test). In order to compare results between patients, we normalized HIV-1 VL values to a mammalian house-keeping gene, ABL. In addition, we immunohistochemically stained lymph node tissue sections for T-cell subsets: CD3, CD4, CD8 and for Treg markers: LAG-3, FOXP3. Positive cells were enumerated using a counting grid. Plasma HIV VL was obtained from patients' medical records.
Results: Among 20 HIV+ patients, 12 LN biopsies were performed less than 1 month (median 0.3, range 0-1) after the plasma VL (Group A), and 8 LN biopsies were performed more than 2 months (median 19, range 2-60) after the plasma VL (Group B). The LN VL in group B was 4.7 times greater than in group A (309040 vs. 66585, p <0.05). The LN LAG-3/CD4 and FOXP3/CD4 ratios were 7.3 and 2.2 fold greater in group B than in group A. However, there was no significant difference between plasma VL in groups A and B. In group A, there was no correlation between LN HIV VL and any other parameters studied. In contrast, in group B, the LN VL was significantly correlated with plasma VL (r, 0.887; p, 0.003), LN CD8 count (r, 0.8; p, 0.017), LN LAG-3/CD4 ratio (r, 0.8; p, 0.017) and FOXP3/CD4 ratio (r, 0.759; p, 0.029).
Conclusions: LN HIV VL correlated with plasma HIV VL for patients with late-stage, but not early- stage, HIV infection. Our data suggest that Tregs in lymph nodes from HIV+ patients have a greater impact on LN HIV VL in late-stage compared to early-stage disease. We hypothesize that Tregs in lymph nodes are recruited and/or activated during chronic/persistent HIV infection.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 148, Tuesday Afternoon