CD8+ T lymphocytes producing Th2-type cytokines (Tc2) in HIV-infected individuals.
Unusual high proportions of CD8+ T-cell clones able to produce IL-4, but no IFN-gamma (Tc2 cells), were generated from both skin biopsies and peripheral blood of HIV-infected individuals in advanced phase of infection. Tc2 cells showed unusual phenotypic and functional features, such as CD30 expression, B-cell helper activity for IgE synthesis and reduced cytolytic potential. Cloning CD8+ T-cell from HIV-infected individuals in autologous feeder cells resulted in a marked increase of CD8+ T-cell clones showing a Tc2 profile. The addition in bulk culture before cloning of both IL-12 and a neutralizing anti-IL-4 antibody dramatically reversed the cytokine profile of CD8+ T-cell clones of HIV-infected individuals to the classic Tc1 pathway. Finally, cloning CD8+ T-cells from healthy HIV-seronegative donors in the presence of feeder cells from HIV-infected individuals resulted in the development of enhanced proportions of CD8+ T-cell clones able to produce IL-4. These data suggest that CD8+ T-cells from HIV-infected individuals can develop into Tc2 cells likely because of either the defective production of IL-12 by HIV-infected macrophages and/or other microenvironmental conditions favoring early IL-4 production. The Tc2 shift during HIV infection may play some role in the reduced defence against viral infections, including HIV itself, in patients with AIDS.
Maggi
E
E
Division of clinical Immunology and Allergy, University of Florence, Italy.
Manetti
R
R
Annunziato
F
F
Romagnani
S
S
D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D016207:Cytokines / Q000096:biosynthesis*; D015658:HIV Infections / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis; D007589:Job Syndrome / Q000150:complications / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D012514:Sarcoma, Kaposi / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology / Q000821:virology; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology
D016207:Cytokines; D016898:Interferon-alpha; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma