Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 1999 Oct 12;96(21):11986-91.
doi: 10.1073/pnas.96.21.11986.

Spontaneous and antigen-induced production of HIV-inhibitory beta-chemokines are associated with AIDS-free status

A Garzino-Demo  1 , R B Moss, J B Margolick, F Cleghorn, A Sill, W A Blattner, F Cocchi, D J Carlo, A L DeVico, R C Gallo
Affiliations
Multicenter Study

Spontaneous and antigen-induced production of HIV-inhibitory beta-chemokines are associated with AIDS-free status

A Garzino-Demo et al. Proc Natl Acad Sci U S A. .

Abstract

The beta-chemokines RANTES, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta suppress infection by macrophage-tropic strains of HIV and simian immunodeficiency virus (SIV) by binding and down-regulating the viral coreceptor, CCR5. Accordingly, we have examined whether higher levels of CCR5 ligands are associated with a more favorable clinical status in AIDS. A cross-sectional study of 100 subjects enrolled in the Multicenter AIDS Cohort Study at the Baltimore site was conducted to measure chemokine production and lymphocyte proliferation by peripheral blood mononuclear cells (PBMC). Statistical analyses of the data revealed that the production of HIV-suppressive beta-chemokines by HIV antigen-stimulated PBMC was significantly higher in HIV-positive subjects without AIDS compared with subjects with clinical AIDS. Increased chemokine production was also correlated with higher proliferative responses to HIV antigens. Both parameters were significantly lower in the AIDS versus non-AIDS group. Notably, significantly higher levels of MIP-1alpha were also observed with unstimulated PBMC from seronegative subjects at risk for HIV infection released as compared with seropositive and non-Multicenter AIDS Cohort Study seronegative subjects. The association of chemokine production with antigen-induced proliferative responses, more favorable clinical status in HIV infection, as well as with an uninfected status in subjects at risk for infection suggests a positive role for these molecules in controlling the natural course of HIV infection.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Antigen-induced proliferation indices and disease status. Cells (2 × 105) per well of fresh PBMC were cultured in round-bottomed, 96-well plates, as described in Methods, in medium alone or with 10 μg/ml gp120-depleted, inactivated HIV-1 (HIV), 10 μg/ml purified p24 antigen (p24), 10 μg/ml C. albicans (candida), or 20 μg/ml PHA (not shown). After 3 days (for PHA) or 6 days of incubation at 37°C, the cells were labeled with 1 μCi of 3[H]thymidine and harvested, and incorporated label was determined by scintillation counting. Geometric mean cpm were calculated from the triplicate wells with and without antigen. Results were calculated as an LSI, which is the geometric mean cpm of the cells plus antigen divided by the geometric mean cpm of the cells without antigen (medium alone). (Bars = SEM.)
Figure 2
Figure 2
Antigen-induced chemokine production and disease status. Fresh PBMC (1.6 × 106) were cultured as described in Methods in medium alone or with 10 μg/ml gp120-depleted, inactivated HIV-1 (HIV), 10 μg/ml purified p24 antigen (p24), 10 μg/ml C. albicans (candida), or 20 μg/ml PHA (not shown). After 3 days (for PHA) or 6 days of incubation at 37°C, supernatants were collected and assayed for RANTES, MIP-1α, and MIP-1β by ELISA. (Bars = SEM.)
Figure 3
Figure 3
Spontaneous MIP-1α production. Fresh PBMC (1.6 × 106) were cultured as described in Methods in medium alone. After 3 days of incubation at 37°C, supernatants were collected and assayed for MIP-1α by ELISA. On the abscissa, population groups include: Controls, healthy laboratory control; seronegative, MACS non-HIV-1-infected; HIV+ No AIDS, MACS HIV-1-infected, AIDS not diagnosed; HIV+ AIDS, MACS HIV-1-infected with AIDS. The ordinate shows natural logarithm of chemokine production. The difference in MIP-1α production between the non-MACS and the MACS seronegatives is statistically significant. When compared with MACS seronegatives, seropositive subjects without AIDS were found to produce significantly lower levels of MIP-1α. Subjects with AIDS were found to spontaneously release significantly lower levels of chemokines when compared with both MACS and non-MACS seronegatives. Box plots are interpreted as follows: the waist is the median, diagonal lines indicate 95% confidence intervals about the median, lower and upper horizontal lines indicate 25th and 75th percentiles of the distribution, and upper and lower bars indicate the range of the distribution excluding outliers. One subject of the seronegative group, producing outstanding levels of MIP-1α, was not used to compose this figure.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Cocchi F, DeVico A L, Garzino-Demo A, Arya S K, Gallo R C, Lusso P. Science. 1995;270:1811–1815. - PubMed
    1. Bleul C C, Farzan M, Choe H, Parolin C, Clark-Lewis I, Sodroski J, Springer T A. Nature (London) 1996;382:829–833. - PubMed
    1. Oberlin E, Amara A, Bachelerie F, Bessia C, Virelizier J L, Arenzana-Seisdedos F, Schwartz O, Heard J M, Clark-Lewis I, Legler D F, et al. Nature (London) 1996;382:833–835. - PubMed
    1. He J, Chen Y, Farzan M, Choe H, Ohagen A, Gartner S, Busciglio J, Yang X, Hofmann W, Newman W, et al. Nature (London) 1997;385:645–649. - PubMed
    1. Horuk R, Hesselgesser J, Zhou Y, Faulds D, Halks-Miller M, Harvey S, Taub D, Samson M, Parmentier M, Rucker J, et al. J Biol Chem. 1998;273:386–391. - PubMed

Publication types

MeSH terms