       Document 0269
 DOCN  M9590269
 TI    CD4-bearing human thymic dendritic cells as targets for HIV infection.
 DT    9509
 AU    Sotzik F; Shortman K; Lowe M; Coughlan A; Crowe S; Cameron P; Walter and
       Eliza Hall Institute of Medical Research, Royal; Melbourne Hospital,
       Parkville, Victoria.
 SO    Annu Conf Australas Soc HIV Med. 1994 Nov 3-6;6:253 (unnumbered poster).
       Unique Identifier : AIDSLINE ASHM6/95291830
 AB    We sought to isolate an early intrathymic precursor cell population from
       human thymus based on the phenotype of the equivalent cell in the mouse
       thymus, which expresses low levels of CD4 (Wu et al, Nature 349: 71). No
       clear cell population with the expected phenotype was found in human
       thymus. However a CD4+ human thymic dendritic cell population was
       isolated which was class II MHChi class I MHChi CD44+1-2-3-7-8-16-34-,
       and negative for monocyte, NK and B cell surface markers. Mixed
       lymphocyte reaction (MLR) and post-culture morphology results are
       consistent with dendritic cells. The expression of CD4 on these
       dendritic cells prompted us to investigate them further as targets for
       HIV infection. They are targets for infection with macrophage tropic but
       not T cell tropic HIV-1 isolates (Ba-L, 676 but not IIIb, 228), as shown
       by PCR for the viral gag gene. The infection was blocked by anti-CD4
       mAbs. Viral p24 was demonstrated in the dendritic cells 5 days after
       pulsing with virus. Transfer of HIV-1 to T cells has been demonstrated
       at 7, 9 and 12 days post infection by assaying for reverse transcriptase
       activity. In conclusion, we have isolated CD4+ human thymic dendritic
       cells which are targets for infection with macrophage (but not T cell)
       tropic isolates of HIV-1. The infection is dependent on CD4 and is
       productive (virus reproduces in DC). Our in vitro data suggests that
       CD4+ DC may transfer virus to developing T cells in thymopoiesis.
 DE    Antigens, CD4/*IMMUNOLOGY/ISOLATION & PURIF  Cells, Cultured  Dendritic
       Cells/*IMMUNOLOGY/VIROLOGY  Human  HIV/*PATHOGENICITY  HIV
       Infections/*IMMUNOLOGY/VIROLOGY  Immunophenotyping
       Macrophages/IMMUNOLOGY/VIROLOGY  Thymus Gland/IMMUNOLOGY/VIROLOGY  Virus
       Replication/IMMUNOLOGY  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

