β-chemokines inhibit activation-induced death of lymphocytes from HIV-infected individuals

The present study investigates the role of the HIV-suppressive β-chemokines macrophage inflammatory protein (MIP)-1α, MIP-1β and RANTES in activation-induced cell death (AICD). A pool of these β-chemokines reduced anti-CD3-induced apoptosis of T cell blasts from healthy blood donors in a dose-dependent manner. Although the pooled β-chemokines were more effective, the inhibitory effect could also be mediated by each of the individual chemokines and was blocked by neutralizing anti-chemokine antibodies. The β-chemokines also inhibited pokeweed mitogen/staphylococcal enterotoxin B-induced T lymphocyte apoptosis in 33/49 HIV-infected (HIV⁺) individuals. This anti-apoptotic effect was not correlated with the patients' CD4 T cell counts. β-chemokines did not lead to altered secretion of IL-2, IL-4, IFN-γ or IL-10 in response to activation stimuli in either normal T cell blasts or peripheral blood mononuclear cells from HIV⁺ individuals. Co-incubation with β-chemokines did not inhibit anti-CD3-induced expression of cell surface Fas ligand, nor did it alter levels of the death receptor Fas or Bcl-2 in T cell blasts, suggesting that the β-chemokines are blocking AICD downstream of Fas. These observations indicate that β-chemokines may play a novel role as modulators of AICD, in addition to their known role as chemoattractants and inhibitors of HIV replication.