Background: CCR5 is a key receptor for HIV infection and has been identified on CD4⁺ lymphocytes in both blood and intestinal mucosa. In seronegative controls, CCR5 expression the peripheral compartment is increased in mucosa compared to in blood. Ffollowing HIV infection, the predominant viral tropism is for the CCR5 receptor and CCR5 expression in blood is increased. correlate with the risk of HIV transmission and The purpose of this study was to determine whether HIV infection results in altered CCR5 co-receptor expression the level of CCR5 expression in intestinal mucosa.

Methods: Mononuclear cells were isolated from blood and intestinal mucosa were obtained from HIV-infected (n = 20) and control subjects (n = 8) and were assessed by flow cytometry for . Flow cytometry was performed to characterize the frequency of 1) Percentage CD4⁺/ CD45⁺, CD8⁺/CD45⁺ and CD4⁺/CCR5⁺ cell populationsphenotypes and 2) Percentage and intensity of CCR5 expression on CD4⁺ cells. Data for cell phenotype are expressed as percentages and the CCR5 receptor intensity. Data for CCR5 median fluorescent intensity (MFI) were log transformed for statistical analysis and reflect the number of CCR5 antibody molecules bound per cell.. In addition, the intensity of CCR5 expression was measured on CD4+ cells.

 

Results: Of the 20 subjects with HIV infection, the mean plasma viral load was 33,766 copies/ml plasma (range < 50–293,864), mean CD4 count was 318 (range 153–612) and all subjects were receiving combination antiretroviral therapy. CD4 lymphopenia was seen in both blood and mucosal samples. An increase in CD8⁺ cells was seen in both compartments. As previously reported, an increase in CD4⁺/CCR5⁺ cells was seen in blood from HIV-infected subjects. However, a significant decrease in CCR5 frequency and MFI was seen in intestinal mucosal samples from the HIV group. Mean values by group are listed below.

 

Cell phenotype	Blood		P value: HIV vs Control	Mucosa		P value: HIV vs Control
	Control	HIV		Control	HIV
CD4+/CD45+	46.7%	22.0%	< 0.0001	29.3%	12.3%	0.001
CD8+/CD45+	20.8%	54.9%	< 0.0001	28.0%	45.7%	0.04
CD4+/CCR5+	21.5%	39.8%	0.005	56.2%	30.8%	0.01
CCR5 MFI	81.1	478.2	NS	164.1	63.5	0.0003

 

Conclusions: In contrast to blood, the key finding of this study is that the frequency and intensity of CCR5 expression on mucosal CD4⁺ lymphocytes is reduced in HIV-infected subjects. This may occur as a response to the increased mucosal levels of Rantes RANTES (the natural ligand of CCR5), which is seen increased in this population of patients. Alternatively, infection of CCR5⁺ cells with HIV may lead to a selective loss of this cell population. Whatever the mechanistic basis of this observation, sufficient CCR5⁺ cells remain to facilitate further cycles of mucosal infection.