T-Regulatory Cells in Lymph Nodes Correlate with HIV Status, Gender, Viral Load and Morphologic Features of Castleman's Disease
J Arce, M Levin, Q Xie, J Albanese, H Ratech. Montefiore Med Ctr/Albert Einstein Coll Med, Bronx, NY; Creighton Univ Med Ctr, Omaha, NE
Background: Lymph nodes from many HIV infected individuals show Castleman's disease (CD)-like changes. These changes could be caused by either immune dysregulation or viral infection. The association of human herpes virus-8 (HHV8) with multicentric CD supports the viral hypothesis. On the other hand, there are only a few studies that have correlated immune dysregulation with lymph node changes. Since FoxP3+ CD4+ T-regulatory cells (T-regs) can impair HIV-specific responses and limit immune activation, we evaluated T-regs in a large number of reactive lymph nodes from both HIV+ and HIV- individuals.
Design: Reactive lymph nodes from 48 HIV+ (20 males; 28 females) and 106 HIV- (40 males; 66 females) individuals were studied for T-regs and T-helper cells by FoxP3 and CD4 antibody staining on tissue microarrays and by counting positive cells in the paracortical T-zone that crossed the lines of a 1 mm2 10x10 grid. Lymph nodes were scored for 6 hyaline vascular and 6 plasma cell morphologic features of CD.
Results: The mean FoxP3+ count per grid, which is proportional to the total number of FoxP3+ cells in the lymph node, was 3 times greater in HIV+ males compared to HIV+ females (23.5 vs 7.8; p=0.0006). Also, HIV+ males compared to HIV- males had almost twice as many FoxP3+ cells (23.5 vs 13.1; p=0.03). On the other hand, HIV+ females compared to HIV- females had fewer FoxP3+ cells (7.8 vs 13.6; p=0.03). HIV+ males compared to HIV+ females had higher viral load (239000 vs 73000; p=0.02), lower peripheral blood CD4 count (262 vs 466; p=0.01), but higher lymph node CD4 count (73.3 vs 28.8; p=0.02), and shorter interval from HIV diagnosis to lymph node biopsy (28 mos vs 93 mos; p=0.04). More morphologic features of the plasma cell variant of CD were seen in lymph nodes from HIV+ compared to HIV- individuals (p=0.007). High FoxP3 counts were associated with plasma cell features in lymph nodes from both HIV+ and HIV- individuals. In 8 lymph nodes, HHV8 was associated with interfollicular plasma cells and increased vascularity (p<0.01).
Conclusions: High T-regs in lymph nodes are associated with high viral load and low peripheral blood CD4 counts. Furthermore, elevated T-regs are associated with the morphologic features seen in CD plasma cell variant. We hypothesize that gender differences in lymph node T-regs might be explained by worse HAART compliance and more high risk behavior in males than females.
Monday, March 9, 2009 11:30 AM
Platform Session: Section D, Monday Morning