AEGiS-11IAC: Raised production of C-C chemokines by CD8+ T cells of long term non-progressor HIV-infected subjects.

11th International AIDS Conference


Vancouver, British Columbia — July 7-12, 1996

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Raised production of C-C chemokines by CD8+ T cells of long term non-progressor HIV-infected subjects.

Int Conf AIDS 1996 Jul 7-12; 11:227 (abstract no. Tu.A.393)
Scala E, Aiuti F, Rosso R, D'Offizi GP, Ferrara R, Paganelli R; Dept. of Clinical Medicine, University La Sapienza, Rome Italy. Fax: +39-644-54621.

OBJECTIVE: The recent description of RANTES, MIP-1alpha and MIP-1beta (C-C chemokines) as the constituents of the HIV-suppressive factor produced by CD8+ lymphocytes of HIV-infected individuals prompted our study of their production by T cell lines (TCL) and clones derived from normal and HIV+ subjects at different disease stages. TCL and clones from healthy donors asymptomatic HIV+ patients with AIDS and Long Term non-Progressors (LTnP) were analysed for surface phenotype, production of C-C chemokines, IL4 and IFNgamma production, in order to define association of chemokines secretion with disease stage, lymphocyte subsets, and cyokine profile.

METHODS: TCL were established by PHA stimulation and culture with rIL2, and cloned by limiting dilution. Supernatants obtained after restimulation with PHA were tested for chemokines, IL4 and IFNgamma by ELISAs. Surface phenotype was determined by cytofluorimetric analysis with mAbs to TCR, CD4 and CD8.

RESULTS: Moderate to high levels of all three chemokines were produced by TCLs of LTnP and asymptomatic HIV+, whereas they were low or absent in normal subjects and AIDS. All these TCLs exihibited a Th1 pattern. A TCL from an AIDS hyper -IgE (HIE) patients produced IL4 and RANTES. CD4 positive clones produced low or moderate levels of these chemokines in asymptomatic HIV+, but only MIP-1beta was detected in normal subjects. The majority of CD8+ clones produced all three chemokines at moderate to high levels, without relationship to IL4 or IFNgamma secretion, as observed in CD4+ cells. In clones from LTnP both RANTES and MIP-1beta were produced at levels similar to normal subjects, but higher than AIDS. Mip-1alpha was significantly increased in CD8+ clones of LTnP compared to AIDS, normal subjects and asymptomatic HIV+. RANTES and MIP-1alpha were also higher in AIDS-HIE compared to asymptomatic HIV+.

CONCLUSIONS: RANTES, MIP-1alpha and MIP-1beta are mainly produced by CD8+ lymphocytes, irrespective of their Th pattern. Clones from LTnP secrete higher amounts of all three chemokines compared to AIDS patients. Among them, MIP-1alpha was producted at higher levels by LTnP compared to all other groups, thus pointing to its possible importance in delaying progression of HIV disease.

Keywords: AEGIS, Chemokines, CC, Antigens, CD8, T-Lymphocytes, Macrophage Inflammatory Protein-1, RANTES, HIV Infections, CD8-Positive T-Lymphocytes, Acquired Immunodeficiency Syndrome, Chemokines, Clone Cells, Antigens, CD4, Interleukin-4, Human, ICA11KWDaegis,chemokines,cc,antigens,cd8,t-lymphocytes,macrophageinflammatoryprotein-1,rantes,hivinfections,cd8-positivet-lymphocytes,acquiredimmunodeficiencysyndrome,chemokines,clonecells,antigens,cd4,interleukin-4,human,ica11

960707
TuA393

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