• Accumulation of DC-SIGN+ CD40+ Dendritic Cells with Reduced CD80 and CD86 Expression in Lymphoid Tissue During Acute HIV-1 Infection
  Abstract 1947
  Authored by K. Lore (Karolinska Institute, Stockholm, Sweden), A. Sonnerborg (Karolinska Institute, Stockholm, Sweden), C. Brostrom (Karolinska Institute, Stockholm, Sweden), Li-Ean Goh (GlaxoSmithKline, London, United Kingdom), L. Perrin (University of Geneva, Geneva, Switzerland), L. Napolitano (University of San Francisco, San Francisco, CA), Y. Van Kooyk (University Medical Centre Nijmegen, Nijmegen, Netherlands), J. Andersson (Karolinska Institute, Stockholm, Sweden)
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Dendritic cells (DC) are the first line of defense in response to HIV infection and are important in the immune system's early recognition of infection. When HIV is first transmitted, the first cells to recognize HIV as a foreign invader are the dendritic cells. HIV is captured on the surface of dendritic cells when it becomes bound by receptors such as CD4, CCR5, CXCR4 and DC-SIGN. The dendritic cells then engulf the HIV and cut it into small pieces that can be easily recognized by specific T cells. Dendritic cells become activated as a result of HIV infection. This activation can be measured by looking for activation markers (CD40, CD80, and CD86) on the surface of these cells. Activated dendritic cells then migrate to the lymph nodes where they in turn activate T cells. Activated CD4 cells are more easily infected with HIV. Thus, the level of dendritic cell activation and resulting CD activation may be important in understanding progression in HIV disease.

This study looks at the level of dendritic cell activation during different stages of HIV disease, comparing its activity in people with acute Epstein-Barr virus (aEBV) infection and in HIV-negative people without an acute infection. Lymph node or tonsilar biopsies were obtained from four HIV-negative controls, four aEBV, six acutely HIV infected patients, seven long term nonprogressors, four chronically-HIV infected, asymptomatic and treated patients, and five patients with AIDS.

Cytokines and cell markers were detected and quantified by in situ immunohistochemistry and image analysis. The results show that mature dendritic cells were located in the same area within lymph nodes as they were in tonsils. There were ten times more dendritic cells in the lymph nodes of those patients with acute HIV and EBV, and slightly less in the long-term nonprogressors, compared to the HIV-negative controls. The number of dendritic cells was markedly reduced in those patients with AIDS. There was an increase in CD40, but not CD80/86 expression during acute HIV. There was an increase in cytokine (IL-1, IL-12, TNF-a, IFN-g) expression during acute HIV infection. The levels of cytokine expression in the other HIV-infected groups were similar to uninfected controls.

This study suggests that dendritic cells exhibit an insufficient expression of CD80/86, probably resulting in a functional defect of mature dendritic cells. The expression of these receptors appears necessary to induce naive CD4 cells in antigen-specific responses. Without sufficient functional CD4 cells to help guide the immune response, there may be a restricted CD8 cytotoxic T-cell response. Because a good CD8-cell response is the most important aspect of containing HIV replication, the dendritic cell defects seen in chronic and advanced HIV disease may offer some insight into why HIV progression occurs. There is no direct application or relevance to clinical practice in this paper. The findings may be useful in designing ways to boost the immune system by correcting the defects found in dendritic cells. If their functional status could be improved, then better CD4 and subsequent CD8 responses could be realized.