Christoph Lange

Publications (2)11.22 Total impact

• Article: Dendritic cell recruitment in response to skin antigen tests in HIV-1 infected individuals correlates with the level of T cell infiltration.

  Frank Liang, Emily Bond, Kerrie J Sandgren, Anna Smed-Sörensen, Molebogeng X Rangaka, Christoph Lange, Richard A Koup, Grace A McComsey, Michael M Lederman, Robert J Wilkinson, Jan Andersson, Karin Loré
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  ABSTRACT: OBJECTIVES:: To study whether in vivo recruitment of dendritic cells (DCs) in response to antigen administration in the skin is altered during HIV-1 infection. DESIGN:: Skin punch biopsies were collected from HIV-1+ as well as seronegative individuals at 48 hours post intradermal injection of inactivated antigens of mumps virus, Candida albicans or purified protein derivate (PPD) from Mycobacterium tuberculosis. METHODS:: Cryosections were analyzed by in situ staining and computerized imaging. RESULTS:: Control skin biopsies showed that there was no difference in the number of skin-resident DCs between seronegative and HIV-1+ individuals. Antigen injection resulted in substantial infiltration of DCs compared to the frequencies found in donor-matched control skin. In HIV-1+ individuals, CD123+/CD303+ plasmacytoid DCs and CD11c+ myeloid DCs, including the CD141+ cross-presenting subset, were recruited at lower levels compared to healthy controls in response to PPD and mumps but not C. albicans. The level of DC recruitment correlated with the frequencies of T cells infiltrating the respective antigen sites. Ki67+ cycling T cells at the injection sites were much more frequent in response to each of the antigens in the HIV-1+ individuals, including those with AIDS, compared to healthy controls. CONCLUSIONS:: Multiple DC subsets infiltrate the dermis in response to antigen exposure. There was no obvious depletion or deficiency in mobilization of DCs in response to antigen skin tests during chronic HIV-1 infection. Instead, the levels of antigen-specific memory T cells that accumulate at the antigen site may determine the level of DC infiltration.
  AIDS (London, England) 01/2013; · 4.91 Impact Factor
• Article: Plasmacytoid dendritic cells infiltrate the skin in positive tuberculin skin test indurations.

  Emily Bond, Frank Liang, Kerrie J Sandgren, Anna Smed-Sörensen, Peter Bergman, Susanna Brighenti, William C Adams, Senait A Betemariam, Molebogeng X Rangaka, Christoph Lange, Robert J Wilkinson, Jan Andersson, Karin Loré
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  ABSTRACT: Plasmacytoid dendritic cells (pDCs) are rarely present in normal skin but have been shown to infiltrate lesions of infections or autoimmune disorders. Here, we report that several DC subsets including CD123(+) BDCA-2/CD303(+) pDCs accumulate in the dermis in indurations induced by the tuberculin skin test (TST), used to screen immune sensitization by Mycobacterium tuberculosis. Although the purified protein derivate (PPD) used in the TST did not itself induce pDC recruitment or IFN-α production, the positive skin reactions showed high expression of the IFN-α-inducible protein MxA. In contrast, the local immune response to PPD was associated with substantial cell death and high expression of the cationic antimicrobial peptide LL37, which together can provide a means for pDC activation and IFN-α production. In vitro, pDCs showed low uptake of PPD compared with CD11c(+) and BDCA-3/CD141(+) myeloid DC subsets. Furthermore, supernatants from pDCs activated with LL37-DNA complexes reduced the high PPD uptake in myeloid DCs, as well as decreased their capacity to activate T-cell proliferation. Infiltrating pDCs in the TST reaction site may thus have a regulatory effect upon the antigen processing and presentation functions of surrounding potent myeloid DC subsets to limit potentially detrimental and excessive immune stimulation.
  Journal of Investigative Dermatology 08/2011; 132(1):114-23. · 6.31 Impact Factor