TY - JOUR
T1 - Cytokine-induced expression of CD1b molecules by peripheral blood monocytes
T2 - Influence of 3'-azido-3'-deoxythymidine
AU - Giuliani, A.
AU - Tentori, L.
AU - Pepponi, R.
AU - Porcelli, S. A.
AU - Aquino, A.
AU - Orlando, L.
AU - Sugita, M.
AU - Brenner, M. B.
AU - Bonmassar, E.
AU - Graziani, G.
PY - 1997/2
Y1 - 1997/2
N2 - CD1b is a nonpolymorphic, MHC-like molecule, capable of presenting non-peptide antigens (Ags) to CD3+, CD4-, CD8-, αβ or γδT lymphocytes. Previous studies have shown that CD1b can be induced in monocytes/macrophages by GM-CSF+IL-4, and can restrict their presentation of Mycobacterium tuberculosis antigen (Ag) to Ag-specific T cells. Since a number of HIV-positive subjects undergo mycobacterial infections, preliminary studies have been performed to explore whether anti-HIV chemotherapy would influence cytokine-induced CD1b expression in peripheral blood monocytes. The results obtained by treating monocytes with GM-CSF+IL-4, in presence or absence of 3'-azido-3'-deoxythymidine (AZT) showed that: (a) the majority of adherent mononuclear cells (AMNC) collected from peripheral blood of healthy donors, express CD1b molecule on the cell membrane, upon treatment with GMCSF+IL-4; (b) CD1b appearance is mainly due to the de novo induction of CD1b gene expression (as confirmed by Northern blot analysis), rather than to migration of the molecule from the cytoplasm to the plasma membrane (as suggested by Western blot analysis); (c) AZT does not alter the percentage of CD1b+ AMNC treated with the cytokines; (d) however, AZT inhibits cytokine-induced proliferation of AMNC, thus reducing the overall Ag-presenting potential of the host. Our results suggest that the anti-proliferative effect of AZT could depress anti-mycobacteria immunity in AZT-treated subjects, which may have important implication for the clinical outcome of patients harbouring inadequately treated mycobacterial infections.
AB - CD1b is a nonpolymorphic, MHC-like molecule, capable of presenting non-peptide antigens (Ags) to CD3+, CD4-, CD8-, αβ or γδT lymphocytes. Previous studies have shown that CD1b can be induced in monocytes/macrophages by GM-CSF+IL-4, and can restrict their presentation of Mycobacterium tuberculosis antigen (Ag) to Ag-specific T cells. Since a number of HIV-positive subjects undergo mycobacterial infections, preliminary studies have been performed to explore whether anti-HIV chemotherapy would influence cytokine-induced CD1b expression in peripheral blood monocytes. The results obtained by treating monocytes with GM-CSF+IL-4, in presence or absence of 3'-azido-3'-deoxythymidine (AZT) showed that: (a) the majority of adherent mononuclear cells (AMNC) collected from peripheral blood of healthy donors, express CD1b molecule on the cell membrane, upon treatment with GMCSF+IL-4; (b) CD1b appearance is mainly due to the de novo induction of CD1b gene expression (as confirmed by Northern blot analysis), rather than to migration of the molecule from the cytoplasm to the plasma membrane (as suggested by Western blot analysis); (c) AZT does not alter the percentage of CD1b+ AMNC treated with the cytokines; (d) however, AZT inhibits cytokine-induced proliferation of AMNC, thus reducing the overall Ag-presenting potential of the host. Our results suggest that the anti-proliferative effect of AZT could depress anti-mycobacteria immunity in AZT-treated subjects, which may have important implication for the clinical outcome of patients harbouring inadequately treated mycobacterial infections.
KW - AZT
KW - CD1
KW - CD1b
KW - Monocytes
KW - Tuberculosis
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U2 - 10.1006/phrs.1997.0130
DO - 10.1006/phrs.1997.0130
M3 - Article
C2 - 9175583
AN - SCOPUS:18744420729
SN - 1043-6618
VL - 35
SP - 135
EP - 140
JO - Pharmacological Research
JF - Pharmacological Research
IS - 2
ER -