Expansion of rare CD8+ CD28- CD11b- T cells with impaired effector functions in HIV-1-infected patients.
The decline in the number of CD4+ T cells in HIV-1-infected patients is known to be related to the increased number of CD8+CD28- T cells. In this paper, we show that CD8+CD28- T cells from HIV-positive patients have an impaired capability to interact with human endothelial cells. This is due to the dramatic expansion, within this subset, of rare CD11b- cells lacking cell-cell adhesion functions. In 50 HIV-positive patients, 19.5% +/- 6.5% of all T cells were CD8+CD28-CD11b-, whereas only 0.8% +/- 0.4% of all T cells from healthy donors showed this uncommon phenotype. The percentage of circulating CD8+CD28-CD11b- T cells was strongly related to the percentage of CD4+ T cells (r = -0.82). This population is peculiar in terms of HIV infection and was found to possess some characteristics associated with effector functions but its cytotoxic properties were impaired. The percentage of target cells lysed by CD8+CD28-CD11b- was significantly lower than that of cells lysed by its CD11b- counterpart (p <.05) both at low (5:1) or at relatively high (20:1) effector/target ratios. CD8+CD28-CD11b- T cells, which lack the ability to interact with endothelial cells, are likely to accumulate and persist in circulation. The biologic properties of CD8+CD28-CD11b- T cells suggest that these cells might be endstage or aberrant differentiated effector cells. Lack of cell-cell adhesion and impaired cytolytic functions favor the hypothesis of a role for CD8+CD28-CD11b- T cells in the development of immunodeficiency.
Caruso
A
A
Institute of Microbiology, University of Brescia Medical School, Spedali Civili, Brescia, Italy. caruso@master.cci.unibs.it
Fiorentini
S
S
Licenziati
S
S
Alessandri
G
G
Ricotta
D
D
Imberti
L
L
Signorini
S
S
Armenta-Solis
A
A
Garrafa
E
E
Balsari
A
A
Turano
A
A
D018106:CD28 Antigens / Q000097:blood / Q000276:immunology; D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D016207:Cytokines / Q000096:biosynthesis; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D008213:Lymphocyte Activation; D016177:Macrophage-1 Antigen / Q000097:blood / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000097:blood / Q000737:chemistry / Q000235:genetics
D018106:CD28 Antigens; D016207:Cytokines; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054353:Perforin