Cocaine Enhances HIV-1–Induced CD4+ T-Cell Apoptosis

Serum reactivities to a panel of phospholipid antigens, including cardiolipin (CL), phosphatidylserine (PS), sphingomyelin, phosphatidylcholine, and phosphatidylethanolamine, were measured by enzyme-linked immunosorbent assay in 196 human immunodeficiency virus- l+ (HIV-1+) patients with CDC II to IVC clinical disease. Significant levels of IgG to CL, PS, or both were observed in 23 patients lacking evidence of thrombophilic events or any peculiar clinical feature of HIV-1 infection. Fluorescence-activated cell sorting analyses showed that in vitro apoptosis of T cells was increased in patients with high serum anti-PS IgG, whereas the overexpression of Fas/Apo-1 marker was detected in all patients regardless of their antiphospholipid reactivities. Macrophages from patients with significant titers of anti- PS IgG antibodies were not activated by the presence of apoptotic CEM lymphoblasts or by purified anti-PS IgG from the same patients. By contrast, these antibodies greatly improved the effector functions of autologous macrophages in antibody-dependent cellular cytotoxicity (ADCC) assays using 51Cr-labeled CEM cells, whereas polyspecific IgG were unable to induce an equivalent cytotoxicity in all instances. An increasing effect on ADCC was also observed in tests using macrophages from healthy controls to CEM coated with anti-PS IgG. These results support a potential correlation of anti-PS specificity with T-cell apoptosis in HIV-1 infection. Because PS is exteriorized by apoptotic lymphocytes, its persistence may stimulate antibodies which cooperate with macrophages in the clearance of dead cells by an enhanced ADCC mechanism. This interpretation could explain the absence of thrombophilia in HIV-1+ patients with serum elevations of antiphospholipid reactivities.

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Increased apoptosis of peripheral blood T cells following allogeneic hematopoietic cell transplantation

Blood ◽

10.1182/blood.v95.12.3832.012k32_3832_3839 ◽

2000 ◽

Vol 95 (12) ◽

pp. 3832-3839 ◽

Cited By ~ 3

Author(s):

Ming-Tseh Lin ◽

Li-Hui Tseng ◽

Haydar Frangoul ◽

Ted Gooley ◽

Ji Pei ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cell Transplantation ◽

Cell Apoptosis ◽

Hematopoietic Cell Transplantation ◽

Hematopoietic Cell ◽

Allogeneic Hematopoietic Cell Transplantation ◽

Cd4 T Cell ◽

Spontaneous Apoptosis ◽

T Cell Apoptosis

Lymphopenia and immune deficiency are significant problems following allogeneic hematopoietic cell transplantation (HCT). It is largely assumed that delayed immune reconstruction is due to a profound decrease in thymus-dependent lymphopoiesis, especially in older patients, but apoptosis is also known to play a significant role in lymphocyte homeostasis. Peripheral T cells from patients who received HCT were studied for evidence of increased cell death. Spontaneous apoptosis was measured in CD3+ T cells following a 24-hour incubation using 7-amino-actinomycin D in conjunction with the dual staining of cell surface antigens. Apoptosis was significantly greater among CD3+ T cells taken from patients 19-23 days after transplantation (30.4% ± 12.5%,P < .05), and 1 year after transplantation (9.7% ± 2.8%, P < .05) compared with healthy controls (4.0% ± 1.5%). Increased apoptosis occurred preferentially in HLA (human leukocyte antigen)-DR positive cells and in both CD3+/CD4+ and CD3+/CD8+ T-cell subsets, while CD56+/CD3− natural killer cells were relatively resistant to apoptosis. The extent of CD4+T-cell apoptosis was greater in patients with grade II-IV acute graft-versus-host disease (GVHD) (33.9% ± 11.3%) compared with grade 0-I GVHD (14.6 ± 6.5%, P < .05). T-cell apoptosis was also greater in patients who received transplantations from HLA-mismatched donors (39.5% ± 10.4%,P < .05) or HLA-matched unrelated donors (32.1% ± 11.4%, P < .05) compared with patients who received transplantations from HLA-identical siblings (19.6% ± 6.7%). The intensity of apoptosis among CD4+ T cells was significantly correlated with a lower CD4+ T-cell count. Together, these observations suggest that activation of T cells in vivo, presumably by alloantigens, predisposes the cells to spontaneous apoptosis, and this phenomenon is associated with lymphopenia. Activation-induced T-cell apoptosis may contribute to delayed immune reconstitution following HCT.

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