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Selective loss of HIV-specific cytolytic activity in patients with AIDS despite a normal broad cytolytic function. HIV-specific CTL belong to the CD8+DR+ subset with decreased clonogenic potential.


Int Conf AIDS. 1990 Jun 20-23;6(3):145 (abstract no. S.A.255). Unique

OBJECTIVE: To investigate the mechanism(s) responsible for the decrease and ultimately the loss of HIV-1 specific cytolytic activity in patients with AIDS. METHODS: HIV-1 specific cytolytic activity as well as the cytolytic potential of sorted CD8+DR+ and CD8+DR- cells were assessed in a cytotoxicity microassay. Using EBV transformed autologous cell lines infected with recombinant vaccinia vectors expressing envelope, gag, pol and nef proteins of HIV-1(111B). Broad cytolytic potential was assessed by a redirected killing assay using as target cells the P815 cell line and by adding alpha-CD3 mAb. RESULTS: In asymptomatic seropositive patients studied with in vivo expansion of the CD8+DR+ subset (30-60%) we demonstrated that the HIV-1 specific cytolytic activity was restricted to the CD8+DR+ subset, whereas no consistent cytolytic activity was displayed by CD8+DR- cells. Analysis over time of HIV-1 specific cytolytic activity and of cytolytic potential showed that HIV-1 specific cytolytic activity was present in the early stages of HIV-1 infection, whereas CD8+DR+ cells were not cytolytic in the advanced stages of disease (AIDS). On the contrary, no major changes in the cytolytic potential between the early and the advanced stages of disease were detected within either the CD8+DR+ or CD8+DR- subsets. Finally, compared to CD8+DR- lymphocytes, CD8+DR+ cells from the same patient showed a severe reduction in the ability to proliferate in vitro in response to different stimuli and in their clonogenic potential. CONCLUSION: The loss of HIV-1 specific cytolytic activity may result at least in part from a progressive decrease in the pool of HIV-1 specific CTL belonging to the CD8+DR+ subset with decreased clonogenic potential at the same time that the broad cytolytic capability of CD8+ T cells remains intact.

Acquired Immunodeficiency Syndrome/*IMMUNOLOGY Antibodies, Monoclonal/IMMUNOLOGY Cell Line Cell Transformation, Viral Clone Cells *Cytotoxicity, Immunologic Gene Products, gag/IMMUNOLOGY Gene Products, nef/IMMUNOLOGY Gene Products, pol/IMMUNOLOGY Herpesvirus 4, Human/PHYSIOLOGY Human HIV-1/*IMMUNOLOGY HLA-DR Antigens/*IMMUNOLOGY Lymphocyte Transformation T-Lymphocytes, Suppressor-Effector/*IMMUNOLOGY ABSTRACT


Information in this article was accurate in December 30, 1990. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.