Changes in viral expression and cytokine profile induced by a polyantigenic immunomodulator in HIV-infected peripheral blood mononuclear cells.
This is the first time, to our knowledge, that evidence is presented showing that a polyantigenic immunomodulator (PAI), acting as a biological response modifier, can either induce or suppress HIV expression depending on the viral load of infected PBMC. PAI consists of a mixture of inactivated bacteria with influenza virus vaccine. PBMC from HIV-infected patients (asymptomatic, age 22-36, symptomatic, age 30-59 and pediatric, < 2 years old) were co-cultured with PHA-stimulated PBMC from uninfected individuals in medium containing IL-2 and PAI. Parallel co-cultures were carried out in a PAI-free medium. Cultures were fed with PHA-stimulated PBMC from uninfected donors on a weekly basis. HIV-p24 ag and cytokine profiles (IL-1 beta, IL-2, IL-4, IFN-gamma and TNF-alpha) were determined on supernatants on day 14. Peripheral blood samples from each patient were evaluated at the beginning of the experiment as to total CD3, total CD19, CD3/CD4, CD3/CD8, CD16/CD56, CD8/HLA-DR and CD8/CD38 markers through flow cytometry. PAI was able to induce viral expression (up to 11,881 pg/ml of p24 antigen) in cultures showing a low (less than 16 pg/ml) or no viral titer. In contrast, in those cultures with high viral titer (10(2)-10(5) pg/ml), a substantial reduction on the titer was observed upon exposure to PAI. PAI was able to induce the production of IFN-gamma and TNF-alpha while that of IL-4 and IL-1 beta was reduced. The predominant cell type detected in the blood samples of the studied subjects were CD8+, CD8+/CD38+ or CD8+/HLA-DR+.(ABSTRACT TRUNCATED AT 250 WORDS)
Ríos
Z
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Department of Microbiology and Immunology, Universidad Central del Caribe, School of Medicine, Bayamón, Puerto Rico 00960-6032.
Ríos
E O
EO
Garcia
M I
MI
De Leon
C
C
Guzman
L M
LM
Rodriguez
W
W
Romero
D
D
Hunter
R
R
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000367:Age Factors; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007252:Influenza Vaccines / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009699:N-Glycosyl Hydrolases / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000943:Antigens, Differentiation; D007252:Influenza Vaccines; D007376:Interleukin-2; D008222:Lymphokines; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1