Document 0267
 DOCN  M9590267
 TI    Assessment of the role of the costimulatory signal mediated via CD28 in
       HIV immunopathogenesis.
 DT    9509
 AU    Williams LJ; Ffrench RA; Lee S; Stewart GJ; Department of Immunology,
       Westmead Hospital, N.S.W.
 SO    Annu Conf Australas Soc HIV Med. 1994 Nov 3-6;6:255 (unnumbered poster).
       Unique Identifier : AIDSLINE ASHM6/95291832
 AB    Activation of CD4+ T cells requires 2 signals, the first via interaction
       between the TCR/CD3 complex on CD4+ T cells and antigen/MHC class 2
       complex on antigen presenting cells (APC). The 2nd signal is now
       believed to be transmitted by binding of CD28 on CD4+ T cells to
       molecules of the B7 family on APC. It is known that in HIV infection,
       even in the asymptomatic stage, there are functional defects in the CD4+
       T cell population that result in loss of responsiveness to antigens such
       as tetanus toxoid (TT). Since stimulation of normal T cells in the
       absence of 2nd signal leads to anergy, we are investigating the role of
       dysregulation of the CD28/B7 mediated signal in T cells from HIV+
       donors. In addition it has been shown recently that there is a decrease
       in CD28+ T cells during progression to AIDS. Proliferation and cell
       surface expression of CD28 and B7 on peripheral blood mononuclear cells
       (PBMC) were studied in response to a range of recall antigens including
       TT, Flu, Herpes Simplex Virus, the mitogens PHA and pokeweed (PWM) and
       to short peptides corresponding to regions of the HIV envelope and gag
       proteins. These responses were examined in an assay system that provided
       costimulation using a monoclonal antibody (mAb) to CD28. Anti-CD28 mAb
       significantly increased the response to PWM, supporting published
       evidence that T cells from HIV+ individuals have a defect in signalling
       through CD28. We will also present data on the effect of anti-CD28 mAb
       on the proliferative response of these cells to recall antigens and HIV
       peptides.
 DE    Antigens, CD28/*PHYSIOLOGY  Cells, Cultured  CD4-Positive
       T-Lymphocytes/IMMUNOLOGY  Human  HIV/*IMMUNOLOGY  HIV
       Infections/*IMMUNOLOGY  HIV Seropositivity/IMMUNOLOGY  Immunologic
       Memory/IMMUNOLOGY  Lymphocyte Transformation/IMMUNOLOGY  Signal
       Transduction/*IMMUNOLOGY  MEETING ABSTRACT

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