CCR5 In Blood Research Articles

Effect of female genital schistosomiasis and anti-schistosomal treatment on monocytes, CD4+ T-cells and CCR5 expression in the female genital tract.

Background Schistosoma haematobium is a waterborne parasite that may cause female genital schistosomiasis (FGS), characterized by genital mucosal lesions. There is clinical and epidemiological evidence for a relationship between FGS and HIV. We investigated the impact of FGS on HIV target cell density and expression of the HIV co-receptor CCR5 in blood and cervical cytobrush samples. Furthermore we evaluated the effect of anti-schistosomal treatment on these cell populations.DesignThe study followed a case-control design with post treatment follow-up, nested in an on-going field study on FGS.MethodsBlood and cervical cytobrush samples were collected from FGS negative and positive women for flow cytometry analyses. Urine samples were investigated for schistosome ova by microscopy and polymerase chain reaction (PCR).ResultsFGS was associated with a higher frequency of CD14+ cells (monocytes) in blood (11.5% in FGS+ vs. 2.2% in FGS-, p = 0.042). Frequencies of CD4+ cells expressing CCR5 were higher in blood samples from FGS+ than from FGS- women (4.7% vs. 1.5%, p = 0.018). The CD14+ cell population decreased significantly in both compartments after anti-schistosomal treatment (p = 0.043). Although the frequency of CD4+ cells did not change after treatment, frequencies of CCR5 expression by CD4+ cells decreased significantly in both compartments (from 3.4% to 0.5% in blood, p = 0.036; and from 42.4% to 5.6% in genital samples, p = 0.025).ConclusionsThe results support the hypothesis that FGS may increase the risk of HIV acquisition, not only through damage of the mucosal epithelial barrier, but also by affecting HIV target cell populations, and that anti-schistosomal treatment can modify this.

The Frequency of α4β7 high Memory CD4+ T Cells Correlates With Susceptibility to Rectal Simian Immunodeficiency Virus Infection

Integrin α₄β₇(high) (α₄β₇(high)) mediates the homing of CD4⁺ T cells to gut-associated lymphoid tissues, which constitute a highly favorable environment for HIV expansion and dissemination. HIV and simian immunodeficiency virus (SIV) envelope proteins bind to and signal through α₄β₇(high) and during acute infection SIV preferentially infects α₄β₇(high) CD4⁺ T cells. We postulated that the availability of these cells at the time of challenge could influence mucosal SIV transmission and acute viral load (VL). We challenged 17 rhesus macaques with 3000 TCID50 of SIVmac239 rectally and followed the subsets of α₄β₇(high) T cells and dendritic cells (DCs) by flow cytometry in blood and tissues, before and after challenge. We found that the frequency of memory CD4⁺ T cells that expressed high levels of α₄β₇(high) (α₄β₇(high) memory CD4⁺ T cells) in blood before challenge correlated strongly with susceptibility to infection and acute VL. Notably, not only at the time of challenge but also their frequency 3 weeks before challenge correlated with infection. This association extended to the rectal tissue as we observed a strong direct correlation between the frequency of α₄β₇(high) memory CD4⁺ T cells in blood and rectum before and after challenge. The frequency of α4β7 myeloid DCs and α₄β₇(high) CD80⁺ DCs also correlated with infection and acute VL, whereas blood CCR5⁺ and CD69⁺ CD4⁺ T cells could not be associated with infection. Our results suggest that animals with higher frequency of α₄β₇(high) CD4⁺ T cells in circulation and in rectal tissue could be more susceptible to SIV rectal transmission.

Chemokine receptor expression on B cells and effect of interferon-β in multiple sclerosis

We investigated the B-cell expression of chemokine receptors CXCR3, CXCR5 and CCR5 in the blood and cerebrospinal fluid (CSF) from patients in relapse of multiple sclerosis (MS) and in neurological controls. Chemokine receptor expression was also studied in interferon-β-treated patients with relapsing–remitting or secondary progressive MS. We observed significantly higher expression of CXCR3 on B cells in the CSF in active MS than in controls. Patients with active MS also had higher B-cell expression of CCR5 in blood. No major differences between RRMS and SPMS patients were detected, and chemokine receptor expression was not affected by interferon-β treatment.