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Session 24 Oral Abstract Session Antiretroviral Chemotherapy: Pathogenesis of Primary HIV Infection Session Time: Wednesday, 10 am - 12:30 pm Room 6A-B

12:00   99. Accumulation of DC-SIGN+ CD40+ Dendritic Cells with Reduced CD80 and CD86 Expression in Lymphoid Tissue during Acute HIV-1 Infection K. Lore*1,2, A. Sonnerborg2, C. Brostrom2, L. Goh3, L. Perrin4, H. McDade3, H. J. Stellbrink5, B. Gazzard6, R. Weber7, L. A. Napolitano8, Y. van Kooyk9, and J. Andersson2 1 NIAID Vaccine Res. Ctr., NIH, Bethesda, MD; 2Karolinska Inst., Huddinge Univ. Hosp., Stockholm, Sweden; 3GlaxoSmithKline, Middlesex, UK; 4Geneva Univ. Hosp., Switzerland; 5Universitatsklinikum Eppendorf, Hamburg, Germany; 6Chelsea & Westminster Hosp., London, UK; 7Royal Free Hosp., London, UK; 8Univ. of San Francisco, CA; and 9Free Univ. Med. Ctr., Amsterdam, The Netherlands Background: The dendritic cells (DCs) may serve as a target cell for mucosal HIV-1 transmission in addition to their key role in antigen presentation and activation of naïve T cells. The interdigitating DCs in vivo in lymphoid tissue were assessed in HIV-1-infected patients with regard to maturation, expression of cytokines and co-stimulatory molecules in order to evaluate if the impaired expansion of HIV-1-specific CD4+ T cells was due to suboptimal function of the DCs. A comparative analysis was performed in patients with acute EBV infection (aEBV), a self-limited lymphoid infection. Methods: DCs were characterized at the single cell level in cryopreserved biopsies by immunohistochemistry and in situ imaging in LT from patients with acute HIV-1 infection (aHI), antiretroviral-treated patients in the chronic phase, untreated slow progressors (SLP), AIDS patients as well as HIV-1 negative controls and aEBV. Results: A significant increase of mature interdigitating DCs expressing CD1a, S-100b, CD83, and DC-SIGN was found in LT from patients with aHI compared to healthy controls (p<0.02). The aHI also showed a significant increase of IL-1a/b/ra, IFN-a, IL-12p70, and CD40 expressing DCs. The co-stimulatory molecules CD80 and CD86 were however only partially upregulated and found at significantly lower levels as compared to aEBV. Thus, aHI did not generate a complete parafollicular network of CD80/CD86 that was found in aEBV. A quantification of viral RNA and DNA showed that the levels in LT from aHI were significantly higher in LT compared to PBMCs. An increased frequency of interdigitating DCs, albeit lower than in aHI, and low expression of CD80 and CD86 were also detected in SLP and treated aviremic subjects. In contrast, the frequency of DCs and cytokine expression in LT of the AIDS patients was significantly reduced. Conclusions: In the early phase of HIV-1 infection there was an accumulation of DCs to LT comparable to that found in acute EBV infection. However, the up-regulation of CD80 and CD86 expression was significantly higher in aEBV as compared to all stages of HIV-1 infection. This co-stimulatory defect evident already in aHI may have an impact on the development of HIV-1 specific CD4+ T cells in LT. Furthermore, a restricted upregulation of these accessory molecules could not prohibit stimulatory signals resulting in significantly higher viral replication at this site as compared to in PBMCs.

©2002 9th Conference on Retroviruses and Opportunistic Infections