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The Journal of Immunology, 2003, 170: 4260-4266.
Copyright © 2003 by The American Association of Immunologists

Decreased Stimulation of CD4+ T Cell Proliferation and IL-2 Production by Highly Enriched Populations of HIV-Infected Dendritic Cells

Tatsuyoshi Kawamura*, Hiroyuki Gatanaga{dagger}, Debra L. Borris*, Mark Connors{ddagger}, Hiroaki Mitsuya{dagger} and Andrew Blauvelt1,*

* Dermatology Branch and {dagger} Experimental Retrovirology Branch, Center for Cancer Research, National Cancer Institute; and {ddagger} Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892

APC infection and dysfunction may contribute to the immunopathogenesis of HIV disease. In this study, we examined immunologic function of highly enriched populations of HIV-infected monocyte-derived dendritic cells (DC). Compared with uninfected DC, HIV-infected DC markedly down-regulated surface expression of CD4. HIV p24+ DC were then enriched by negative selection of CD4+HIV p24- DC and assessed for cytokine secretion and immunologic function. Although enriched populations of HIV-infected DC secreted increased IL-12p70 and decreased IL-10, these cells were poor stimulators of allogeneic CD4+ T cell proliferation and IL-2 production. Interestingly, HIV-infected DC secreted HIV gp120 and the addition of soluble (s) CD4 (a known ligand for HIV gp120) to DC-CD4+ T cell cocultures restored T cell proliferation in a dose-dependent manner. By contrast, addition of antiretroviral drugs did not affect CD4+ T cell proliferation. Furthermore, recombinant HIV gp120 inhibited proliferation in uninfected cocultures of allogeneic DC and CD4+ T cells, an effect that was also reversed by addition of sCD4. In summary, we show that HIV gp120 produced by DC infected by HIV in vitro impairs normal CD4+ T cell function and that sCD4 completely reverses HIV gp120-mediated immunosuppression. We hypothesize that HIV-infected DC may contribute to impaired CD4+ T cell-mediated immune responses in vivo and that agents that block this particular immunosuppression may be potential immune adjuvants in HIV-infected individuals.




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