RANTES Production in HIV‐1 Antigen‐Stimulated Whole Blood Culture: Relationship with Type 1 Immune Response and Plasma Viral Load in Individuals Infected with HIV‐1

Abstract

Host factors which control replication and clearance of human immunodeficiency virus (HIV) are poorly understood. RANTES (regulated on activation, normal T cell expressed and secreted) and other beta-chemokines may be HIV-1-suppressive factors but their role in the progression of HIV-1 infection is a subject of controversy. We investigated the relationship between production of RANTES and correlates of disease progression in 15 patients infected with HIV-1. We used whole blood culture to study the production of RANTES, interferon (IFN)-gamma, interleukin (IL)-4 and IL-13 in response to supernatant of T cells infected with HIV-1. A defect of RANTES production was associated with a predominant type 2 and decreased type 1 cytokine profile (IL-4 and/or IL- 13 > IFN-gamma). We obtained a positive correlation between RANTES and IFN-gamma (P = 0.004) and the ratio of type 1 and type 2 cytokines IFN-gamma/IL-4 (P = 0.04) and IFN-gamma/IL-13 (P = 0.003), and a negative correlation between RANTES production and HIV-1 RNA copy number in plasma (P = 0.01). The same pattern of correlation was observed between HIV-1 p24-stimulated production of RANTES and the plasma viral load (P = 0.02, n = 15). The measurement of RANTES produced by heparinized whole blood in response to HIV-1 antigens appears as a potentially valuable tool to assess the defect of type 1 immune response in individuals infected with HIV-1 and to define whether the absence of a RANTES response may play a role in the increased rate of HIV-1 replication.

Patterns of Chemokine Expression in Models ofSchistosoma mansoniInflammation and Infection Reveal Relationships between Type 1 and Type 2 Responses and Chemokines In Vivo

“…2 and 3 is similar to what is seen for a number of other chemokines, such as MCP-3, and is, as noted in Results, also consistent with the general pattern of expansion and reduction in granuloma size during this time (34,51). For RANTES, published data have also associated induction with type 1 responses (3,24,26,42). For lymphotactin, there is little information on its expression in models of disease.…”

Chemokine immunobiology in HIV-1 pathogenesis

“…Our preliminary observations have also shown a preferential infection of Th1 and Th2 cells by R5 and X4 isolates, respectively, when viral entry is measured in the first 24 h [156]. However, R5 viral replication and spread in Th1 cells was not as efficient as that in Th2 cells, perhaps due to the increased ␤-chemokine secretion in Th1 cells [32,80,81].…”

“…For example, it has been shown that RANTES can participate in activation of HIV-1-specific CD8 ϩ cytotoxic activity via CCR3 [79] and that MIP-1␣, MIP-1␤, and RANTES are preferentially associated with type 1 immune responses [32,80,81]. That these ␤-chemokines can also preferentially recruit T helper 1 cells to potential sites of inflammation [82,83] suggests the existence of a positive feedback loop that links the production of viral suppressive chemokines to type 1 immune responses.…”

“…CC-chemokines are a predominant product of CD45RO ϩ memory phenotypes with an increased expression within the IFN-␥-secreting cells (type 1) [80,81]. Although expression of CC-chemokines is associated with resistance to R5 HIV-1 infection, expression of CCR5 by CD4 ϩ T cells is not always equally associated with infection efficiency.…”

“…This may be simply due to CCR5 up-regulation by IL-2 [144,167,168] as a result of T cell activation. [32,80,81]. Negative regulatory factors to contain X4 viral replication in type 2 responses have yet to be identified.…”