We have recently described a significant correlation between human immunodeficiency virus-1 (HIV-1) RNA replication and monocyte chemotactic protein-1 (MCP-1) levels in the cerebrospinal fluid (CSF) of individuals with the acquired immunodeficiency syndrome (AIDS) with HIV encephalitis (E). Because local macrophages (microglia) are the cells predominantly infected in the brain, we investigated whether in vitro HIV infection affects MCP-1 production in mononuclear phagocytes (MP). MCP-1 secretion and expression were consinstently upregulated over constitutive levels in human monocyte-derived macrophages (MDM) infected with the M-tropic R5 BaL strain of HIV-1. HIV replication was required for this effect, as demonstrated by the absence of chemokine upregulation after infection in the presence of 3’-azido-3’-deoxythimidine (AZT) or cell-exposure to heat-inactivated (▵°) virus. MCP-1 induction was not restricted to HIV-1 BaL, but was also observed during productive infection of MDM with two primary isolates differing for entry coreceptor usage and of U937 cells with the X4 HIV-1 MN strain. Based on the observation that exogenous HIV-1 Tat induced MCP-1 expression in astrocytes, we also investigated its role in MDM and U937 cells. Exogenous Tat induced MCP-1 production from MDM in a concentration-dependent manner, however, it was not effective on uninfected U937 cells or on the chronically infected U937-derived cell line U1. Transfection of Tat-expressing plasmids moderately activated HIV expression in U1 cells, but failed to induce MCP-1 expression in this cell line or in uninfected U937 cells. HIV replication-dependent expression of MCP-1 in MP may be of particular relevance for the pathogenesis of HIV infection in nonlymphoid organs such as the brain.

CD30 is a member of the TNF receptor superfamily, previously shown to be expressed on Hodgkin's lymphoma cells and on normal activated lymphocytes. We here show that CD30 is highly expressed on recently activated human γ δ T cells. Elevated surface levels of this molecule persisted in long‐term cultures of γ δ cells, without further cell stimulation. CD30 acted as a co‐stimulus in γ δ T cells by potentiating the intracellular Ca2+ fluxes induced by CD3 cross‐linking. The engagement of CD30 enhanced the expression of several cytokines induced upon CD3 stimulation such as IL‐4 and IFN‐γ but not IL‐10. The CC chemokines RANTES and macrophage inflammatory protein‐1β were constitutively expressed and not affected by stimulation. The inducible expression of the neutrophil chemoattractant IL‐8 was enhanced by CD30 co‐stimulation, as well as that of the CC chemokines I‐309 and MDC, whereas the secretion of the monocyte chemotactic protein‐1 was not detected. Triggering of CD30 may therefore modulate the expression of several cytokines released by γ δ cells; the expression of its physiologic ligand by APC and neutrophils at the site of infection may contribute to determine the outcome of an immune response.

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