       Document 0806
 DOCN  M9460806
 TI    Role of interleukin-10 in T helper cell dysfunction in asymptomatic
       individuals infected with the human immunodeficiency virus.
 DT    9404
 AU    Clerici M; Wynn TA; Berzofsky JA; Blatt SP; Hendrix CW; Sher A; Coffman
       RL; Shearer GM; Experimental Immunology Branch, National Cancer
       Institute,; National Institutes of Health, Bethesda, Maryland 20892.
 SO    J Clin Invest. 1994 Feb;93(2):768-75. Unique Identifier : AIDSLINE
       MED/94157097
 AB    The loss of T helper cell (TH) function in asymptomatic HIV type
       1-infected individuals occurs before the decline in CD4+ T cells. At
       least part of the loss in TH function results from changes in
       immunoregulatory cytokine profiles. To investigate the role of IL-10 in
       such dysregulation, we tested whether: (a) expression of IL-10-specific
       mRNA would be upregulated in PBMC from asymptomatic, HIV-infected (HIV+)
       individuals; (b) PBMC from these same individuals would produce
       increased levels of IL-10 when stimulated in vitro with
       phytohemagglutinin; and (c) defective antigen-specific TH function could
       be restored by anti-IL-10 antibody. We observed that IL-10-specific mRNA
       was marginally upregulated, and increased levels of IL-10 were produced
       by PBMC from HIV+ individuals compared with PBMC from uninfected
       individuals. Those individuals whose TH function was more severely
       compromised produced higher levels of IL-10. Additionally, defective
       antigen-specific TH function in vitro could be reversed by anti-IL-10
       antibody, including the response to HIV envelope synthetic peptides.
       Furthermore, the antigen-specific TH responses of HIV-uninfected PBMC
       could be reduced with IL-10, a process reversed by anti-IL-10. These
       results confirm that the early loss of TH function in HIV+ individuals
       is due at least in part to cytokine-induced immune dysregulation, and
       support the hypothesis of a switch from a predominant type 1 state to a
       predominant type 2 condition in HIV infection.
 DE    Antigens, CD/ANALYSIS  Cells, Cultured  Gene Expression  Human  HIV
       Infections/*IMMUNOLOGY  HIV Seropositivity/*IMMUNOLOGY
       Immunophenotyping  Interleukin-10/*BIOSYNTHESIS/PHARMACOLOGY/*PHYSIOLOGY
       Interleukin-2/BIOSYNTHESIS  Lymphocyte Transformation
       Lymphocytes/*IMMUNOLOGY  RNA, Messenger/BIOSYNTHESIS/METABOLISM
       Support, Non-U.S. Gov't  T-Lymphocytes/DRUG EFFECTS/*IMMUNOLOGY
       T-Lymphocytes, Helper-Inducer/*IMMUNOLOGY  JOURNAL ARTICLE

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

