C-C chemokines, IL-16, and soluble antiviral factor activity are increased in cloned T cells from subjects with long-term nonprogressive HIV infection.
A combination of three beta, or C-C, chemokines, as well as IL-16, have been shown to inhibit HIV replication in vitro. Cellular antiviral factor is a more potent agent, and acts on all HIV strains. All are mainly, but not exclusively, produced by CD8+ T cells, both in HIV+ and healthy subjects. We studied the production of these HIV-suppressive factors in patients with HIV infection at different stages of disease. No difference in production by PBMC stimulated with PHA has been observed in asymptomatic HIV+, long-term nonprogressors (LTnP), and AIDS patients. When T cell line supernatants from these three groups were studied, no significant difference was found for C-C chemokines or IL-16 production, and viral suppression. However, T cell clones from LTnP secreted higher levels of all three chemokines, IL-16, and exerted a stronger inhibition on HIV replication. CD8+ clones showed a higher production than CD4+ clones. These clones were able to produce all antiviral factors irrespective of the secretion of type 1 or type 2 cytokines. The antiviral activities were not correlated, implying that viral suppression did not depend solely on C-C chemokines or IL-16. We postulate that all factors are needed to prevent HIV disease progression.
Scala
E
E
Department of Clinical Medicine, University La Sapienza, Rome, Italy.
D'Offizi
G
G
Rosso
R
R
Turriziani
O
O
Ferrara
R
R
Mazzone
A M
AM
Antonelli
G
G
Aiuti
F
F
Paganelli
R
R
D000998:Antiviral Agents / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D002999:Clone Cells; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D019410:Interleukin-16 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D013997:Time Factors
D000998:Antiviral Agents; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D019410:Interleukin-16; D019402:Macrophage Inflammatory Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015847:Interleukin-4; D007371:Interferon-gamma