Impact of TNF alpha, LT alpha, Fc gamma RII and complement receptor on HIV-1 trapping in lymphoid tissue from HIV-infected patients

Objectives: To investigate HIV trapping mechanisms in patients with acute i nfection and in asymptomatic individuals prior to and during antiretroviral therapy. To determine the role of complement receptor (CR), Fc gamma recep tor II (Fc gamma RII), tumour necrosis factor alpha (TNF alpha), and lympho toxin alpha (LT alpha) expression in HIV trapping efficiency. Methods: Lymphoid tissues from three acutely HIV-infected patients and six asymptomatic, chronically HIV-infected patients collected prior to and duri ng antiretroviral therapy were compared with lymphoid tissues from six HIV- seronegative subjects. HIV, TNF alpha and LT alpha RNA expression was detec ted and quantified by fluorescence in situ hybridization. CR, Fc gamma RII and HIV p24 antigen were detected and quantified by fluorescence immunohist ochemistry. Results: The amount of trapped HIV did not differ significantly between pat ients with acute HIV infection and asymptomatic individuals, and was indepe ndent of the presence of CR or Fc gamma RII expression. However, in patient s with acute infection, the amount of trapped virus was correlated inversel y with the number of HIV-infected cells (P = 0.0092) and with the size of t he light zone (P = 0.037). In these patients, the number of TNF alpha -expr essing cells was correlated inversely with the amount of trapped virus (P = 0.014) and positively correlated with the size of the light zone in germin al centers (P = 0.041). No correlations were observed between TNF alpha or LT alpha expression and Fc gamma RII or CR expression. Conclusion: This report provides the first evidence that in humans TNF alph a is involved in the development of lymphoid follicles, HIV trapping, and, consequently, in early host immune responses. A model is proposed for early events in patients during acute HIV infection. (C) 2000 Lippincott William s & Wilkins.