610 Medizin und Gesundheit
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Human immunodeficiency virus (HIV-1) infection in the human brain Ieads to characteristic neuropathological changes, which may result indirectly from interactions of the envelope glycoprotein gp 120 with neurons and/or glial cells. We therefore investigated the binding of recombinant gp120 (rgp120) to human neural cells and its effect on int~acellular.s.ignallin~. Herewe pre~ent evidence that rgp120, besides binding to galactocerebroside or galactosyl-sulfatlde, spec1f1cally bmds to a protem receptor of a relative molecular mass of approximately 180,000 Da (180 kDa) pre~ent. on the CD4-negative glioma cells D-54, but not on Molt4 T lymphocytes. Binding of rgp120 to this receptor rap1dly 1nduced a tyrosine-specific protein kinase activity leading to tyrosine phosphorylation of 130- and 115-kDa p~oteins. The c~ncentration of intracellular calciumwas not affected by rgp120 in these cells. Our data suggest a novel Signal transduc1ng HIV-1 gp120 receptor on CD4-negative glial cells, which may contribute to the neuropathological changes observed in HIV-1-infected brains.
Cutaneous leishmaniasis is initiated by the bite of an infected sandfly and inoculation of Leishmania major parasites into the mammalian skin. Macrophages are known to playa central role in the course of infection because they are the prime host cells and funetion as antigen-presenting eells (APC) for induetion of the eell-mediated immune response. However, in addition to maerophages in the dermis. the skin eontains epidermal Langerhans eells (LC) which ean present antigen (Ag) to T cells. Therefore, using a murine model of cutaneous leishmaniasis, we analyzed the ability of epidermal cells to induce a T eell response to L.major. The results demonstrated that freshly isolated LC, but not cuItured LC, are highly active in presenting L.major Ag in vitro to T cells from primed mice and to a L.major-specific T cell clone. Furthermore, freshly isolated LC had the ability to retain L.major Ag in immunogenic form for at least 2 days. Their efficiency was much greater than that of irradiated spleen cells, a standard population of APC. LC stimulated both T cell proliferation and production of the Iymphokines interleukin (IL)-2 and IL-4. The response was Ag specific and could be induced by lysate of L. major parasites and by live organisms. The data suggest that epidermal LC are important APC in eutaneous leishmaniasis. They may perform a critical funetion by eapturing L.major Ag in the skin and presenting it either to quiescent T eells circulating through the draining lymph node or locally to T effector cells infiltrating the cutaneous lesion.