Defective uptake of alpha-fetoprotein (AFP) and transferrin (Tf) by PHA-activated peripheral blood lymphocytes from patients with AIDS and related syndromes.
Serum alpha-fetoprotein (AFP) and transferrin (Tf) are actively endocytosed by many growing cells during ontogenic and neoplastic growth, but also by peripheral T lymphocytes upon mitogen activation. AFP and Tf uptake occurs through receptor-mediated endocytosis. The purpose of the present work was to assess whether the expression and functional activity of AFP and Tf receptors are impaired in mitogen-activated T cells from several groups of HIV-1 seropositive (HIV+) individuals. Forty HIV+ cases were studied, including 12 patients with AIDS, 12 with lymphoadenopathy syndrome (LAS), as well as 16 asymptomatic homosexuals (As). Quantification of AFP and Tf uptake was carried out by fluorescence-activated cell sorting (FACS) using fluoresceinated derivatives of these proteins. Compared with healthy blood donors, the three HIV-1 seropositive groups exhibited clear impairment in the ability of their peripheral blood mononuclear cells (PBMC) to internalize AFP and Tf. The decrease in mean values of AFP uptake correlates roughly with the severity of the clinical status. Although these observations need to be confirmed after a much wider study groups, the AFP-Tf-endocytosis assay presented here clearly reveals early defective functions of mitogen-responsive T cells in disease-free subjects and may provide the basis for a prognostic test. The pathophysiological implications of these facts are discussed in relation to the structural and/or metabolic activities of fatty acids and iron, the ligands carried by AFP and Tf, respectively.
Laboratoire de Chimie des Protéines, Institut de Recherches Scientifiques sur le Cancer, Villejuif, France.
J
J
Uriel
Y
Y
Lunardi-Iskandar
J
J
Laborda
J M
JM
Torres
J
J
Naval
V
V
Georgoulias
R
R
Lowi
C
C
Jasmin
Z
Z
Mishal
D000386:AIDS-Related Complex / Q000378:metabolism*; D000163:Acquired Immunodeficiency Syndrome / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism*; D000509:alpha-Fetoproteins / Q000378:metabolism*
D010835:Phytohemagglutinins; D014168:Transferrin; D000509:alpha-Fetoproteins