       Document 0784
 DOCN  M9550784
 TI    Lack of correlation between phenotype activation markers of CD8
       lymphocytes and cytotoxic T lymphocyte (CTL) function in HIV-1
       infection: evidence for rescue with rIL-2.
 DT    9505
 AU    Chia WK; Nisbet-Brown E; Li X; Salit I; Joshi S; Read SE; Department of
       Microbiology, University of Toronto, Ontario,; Canada.
 SO    Viral Immunol. 1994;7(2):81-95. Unique Identifier : AIDSLINE
       MED/95151138
 AB    CTL activity against HIV-1 antigens expressed on HLA-A-matched
       EBV-transformed B target cells was detected in 33% (6/18) of freshly
       isolated PBMC (FPBMC) from patients in the early stages of HIV-1
       infection (CDCII). No CTL activity was detected in FPMBC in patients
       with AIDS (CDCIV). However, the presence of CTL activity did not
       correlate with the expression of CTL activation markers. A dual-color
       flow cytometric examination revealed that the CD8+ lymphocytes bearing
       the memory (CD29) and activation (S6F1) surface molecules increased in
       number as the HIV-1 infection progressed. This functional and phenotypic
       discrepancy in memory CD8+ lymphocytes suggests that the memory CD8+
       lymphocytes have lost cytotoxic function and become paralyzed as the HIV
       disease progresses. Incubation of PBMC of HIV(+) patients with rIL-2
       reactivated predominantly HIV-specific CTL. However, rIL-2 stimulation
       also activated a polyclonal or polyreactive cytotoxic function. The
       reactivation of CTL function is rIL-2 dosage dependent and the amount of
       rIL-2 required for reactivation is associated with the severity of the
       disease. HIV antigen specific CTL in HIV(+) patients can be selectively
       expanded by HIV antigen stimulation in the presence of rIL-2. These
       results suggest that the in vivo IL-2 deficiency occurring in HIV-1
       infection may be responsible in part for the paralysis of HIV specific
       CTL activity. Such activity can be rescued nonspecifically by exogenous
       rIL-2 stimulation and expanded specifically by HIV-1 antigen
       stimulation.
 DE    Antigens, Surface/IMMUNOLOGY  Cytotoxicity, Immunologic/IMMUNOLOGY
       CD4-Positive T-Lymphocytes/IMMUNOLOGY  CD8-Positive
       T-Lymphocytes/*IMMUNOLOGY  Flow Cytometry  Human  HIV
       Antigens/IMMUNOLOGY  HIV Infections/*IMMUNOLOGY  HIV-1/*IMMUNOLOGY
       HLA-A Antigens/IMMUNOLOGY  Immunologic Memory/IMMUNOLOGY
       Immunophenotyping  Interleukin-2/IMMUNOLOGY  Lymphocyte
       Transformation/*IMMUNOLOGY  Recombinant Proteins/IMMUNOLOGY  Support,
       Non-U.S. Gov't  T-Lymphocytes, Cytotoxic/*IMMUNOLOGY  JOURNAL ARTICLE

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

