Summ~aryDuring human immunodeficiency virus (HIV) infection there is a profound and selective decrease in the CD4 + population of T lymphocytes. The mechanism of this depletion is not understood, as only a small fraction of all CD4 + cells appear to be productively infected with HIV-1 in seropositive individuals. In the present study, crosslinking of bound gp120 on human CD4 + T cells followed by signaling through the T cell receptor for antigen was found to result in activation-dependent cell death by a form of cell suicide termed apoptosis, or programmed cell death. The data indicate that even picomolar concentrations of gp120 prime T cells for activationinduced cell death, suggesting a mechanism for CD4 + T cell depletion in acquired immune deficiency syndrome (AIDS), particularly in the face of concurrent infection and antigenic challenge with other organisms. These results also provide an explanation for the enhancement of infection by certain antibodies against HIV, and for the paradox that HIV appears to cause AIDS after the onset of antiviral immunity.T he immunodeficiency that defines AIDS is due primarily to a progressive decline in the number and function of CD4 + T cells. The mechanism of this decline is debated, though lyric infection of cells targeted by interaction of CD4 with the envelope glycoprotein of the HIV virion, gp120, is an obvious model (1-4), and recent data suggest an apoptotic mechanism of cell death after HIV infection (5). However, previous studies have found that only 1 in 1-10 x 104 PBMC actively express HIV-1 in patients with AIDS (6-10), and immune dysfunction is seen early in infection, before a significant proportion of CD4 + cells has been eliminated (11-15). Thus, it is likely that mechanisms other than direct viral destruction contribute to CD4 + T cell loss and to the anergy associated with CD4 + T cell-dependent immune responses.Mouse splenic T cells pretreated with anti-CD4 antibodies die by apoptosis when stimulated through the oL/~ TCR (16). Apoptosis is an active form of physiologic cell death, requiring RNA and protein synthesis, which is characterized by the activation of endogenous endonucleases that cleave chromatin DNA between nucleosomes (17, 18). Here we report that crosslinking of gp120 on human CD4 + T cells followed by signaling through the TCR results in activation-induced cell death. This cell death has the characteristic features of apoptosis, including the histologic changes of nuclear and cytoplasmic condensation and DNA fragmentation into nucleosome-sized multimers of 200 bp. Our data provide a mechanism for the recent observation that CD4 + T cells from HIV-infected individuals are primed in vivo for suicide by apoptosis, upon TCR activation by both superantigen and MHC class II-restricted antigens (19). Materials and Methodslsola~'on ofCD4 + T Cells. Human T ceils were separated from Ficoll-Hypaque-isolated PBMC by rosetting with 2-aminoethylisothio-uronium bromide hydrobromide (AET)-treated SRBC, as described (20). CD4 + calls were isolated by incu...

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Enteral glutamine supplementation in adult burn patients reduces blood infection by a factor of three, prevents bacteremia with P. aeruginosa, and may decrease mortality rate. It has no effect on level of consciousness and does not appear to influence phagocytosis by circulating polymorphonuclear cells.

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