       Document 0082
 DOCN  M9610082
 TI    Markers of immune cell activation and disease progression. Cell
       activation in HIV disease.
 DT    9601
 AU    Peakman M; Mahalingam M; Pozniak A; McManus TJ; Phillips AN; Vergani D;
       Department of Immunology, King's College School of Medicine,; London,
       United Kingdom.
 SO    Adv Exp Med Biol. 1995;374:17-26. Unique Identifier : AIDSLINE
       MED/96047234
 AB    Immune cell activation is a feature of infection with the human
       immunodeficiency virus (HIV). Here we report our studies on a cohort of
       over 400 patients with HIV infection studied cross-sectionally and
       longitudinally to examine the relationship between markers of immune
       cell activation and disease progression. To examine disease progression,
       340 patients with HIV infection but without AIDS were followed for a
       total of 574 patient years, during which 56 developed AIDS. In our first
       study, 157 patients in CDC groups II-IV were examined cross-sectionally
       for in vivo expression of the activation markers HLA-DR and CD25 on CD3,
       CD4 and CD8 T cells. Levels of CD3+ HLA-DR+ T cells are high in HIV
       infection and show a significant negative correlation with CD4 counts (r
       = 0.52; p < 0.001). The appearance of HLA-DR+ CD3+ T cells is an early
       feature of asymptomatic HIV+ patients, with a greater proportion (82%)
       showing abnormally high levels of these than abnormally low levels of
       CD4 (52%; p < 0.001). Examining activation of the CD4 subset
       specifically is likely to be of greater interest, given that this cell
       is the viral target. Indeed, we found that in the cross-sectional study,
       levels of HLA-DR+ and CD25+ CD4 lymphocytes show a step-wise linear
       increase with increasing disease severity (significant test for linear
       trend; p < 0.001). In our previous studies, only declining CD4 count has
       shown such a significant linear trend. These data suggest that measuring
       activated CD4+ T cells in the periphery may be a powerful predictive
       tool. In our second study, we examined the expression of other markers
       acquired (CD45R0) and lost (CD45RA) following activation of naive T
       cells. Examining expression of these on CD4 and CD8 cells
       cross-sectionally in 71 HIV+ patients, we found abnormalities in
       percentage levels of CD45RA+ and CD45R0+ populations, none of which
       showed any relationship to disease severity. Intriguingly, however, we
       noted that the surface density of both CD45RA and CD45R0 molecules on
       CD4 and CD8 cells was markedly and significantly reduced at all stages
       of HIV infection (eg relative specific fluorescence reduced by up to
       50%; p < 0.001). This abnormality was confirmed in studies using
       antibodies to a common epitope on all CD45 isoforms (pan-CD45) and to
       the CD45RB isoform. Finally, returning to the question of immune cell
       markers of activation and disease progression, we have examined some of
       the best documented markers in our longitudinal study.(ABSTRACT
       TRUNCATED AT 400 WORDS)
 DE    Adult  Biological Markers/BLOOD  Case-Control Studies  Disease
       Progression  Female  Follow-Up Studies  Human  HIV
       Infections/*IMMUNOLOGY  Immunologic Memory  Lymphocyte Transformation
       Male  Support, Non-U.S. Gov't  T-Lymphocyte Subsets/*IMMUNOLOGY  JOURNAL
       ARTICLE

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

