Type 1 cytokine production and low prevalence of viral isolation correlate with long-term nonprogression in HIV infection.
Cytokine production, prevalence of viral isolation, and surface marker expression of peripheral blood mononuclear cells (PBMCs) were analyzed in HIV+ individuals with different patterns of disease progression to establish correlations between these parameters. Thus, mitogen-stimulated in vitro production of interferon gamma (IFN-gamma) and interleukin 2 (IL-2) (type 1 cytokines), and of IL-4 and IL-10 (type 2 cytokines) as well as prevalence of viral isolation were evaluated in 26 HIV+ long-term nonprogressors (LTNPs), in 28 HIV+ patients with progressive HIV infection (PI), and in 24 HIV-seronegative controls (HCs). Surface expression of activation and nonactivation markers was also analyzed in a group of these donors. We report that (1) IL-2 and IFN-gamma production is reduced and IL-4 and IL-10 production is increased in PI patients compared to HCs and LTNPs; (2) prevalence of HIV isolation is lower in LTNPs compared to PI, and the primary viral isolates in LTNPs show a slow/low (S/L) phenotype; and (3) the elevated production of type 2 cytokines is paralleled by an increase in CD57+CD4+CD7- lymphocytes. Thus, whereas a high IL-2, high IFN-gamma/low IL-4, low IL-10 cytokine production pattern is present in HC and in LTNP HIV+, progression of HIV infection is associated with a low IL-2 low IFN-gamma/high IL-4, high IL-10 cytokine profile; increased prevalence of HIV isolation; and an augmented percentage of CD57+CD4+CD7- lymphocytes. These findings further confirm that a dominant type 1 cytokine profile together with reduced prevalence of virus isolation is associated with lack of progression in HIV infection.
Clerici
M
M
Cattedra di Immunologia, Università degli Studi di Milano, Ospedale L. Sacco, Italy.
Balotta
C
C
Meroni
L
L
Ferrario
E
E
Riva
C
C
Trabattoni
D
D
Ridolfo
A
A
Villa
M
M
Shearer
G M
GM
Moroni
M
M
Galli
M
M
D000163:Acquired Immunodeficiency Syndrome / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D015331:Cohort Studies; D016207:Cytokines / Q000096:biosynthesis*; D005434:Flow Cytometry; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007700:Kinetics; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D010835:Phytohemagglutinins / Q000494:pharmacology; D017741:Survivors; D016176:T-Lymphocyte Subsets / Q000166:cytology
D016207:Cytokines; D007376:Interleukin-2; D010835:Phytohemagglutinins; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma