(P4) Impaired homing properties of CD8+ T cells in HIV-1 infected patients receiving early anti-retroviral therapy


Petkov S[1], Nasi A[1], Bekele Y[1], Hejdeman B[2], Chiodi F[1]


1. Department of Microbiology, Tumor and Cell Biology at Biomedicum, Karolinska Institutet, Solnavägen 9, 171 65 Solna, Sweden. 2. Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet and Unit of Infectious Diseases, Venhälsan, Södersjukhuset, Stockholm, Sweden.


The number of CD8+ T cells is increased in the blood of HIV-1 infected patients and antiretroviral treatment (ART) initiated during the chronic phase of infection has a limited effect in reverting this pathological phenomenon which can be associated to non-AIDS related diseases. The mechanism of CD8+ T cell expansion in patients is poorly characterized.

Using flow cytometry we assessed whether expression of chemokine receptors mediating homing of CD8+ T cells to the gut and inflamed tissues could be altered during HIV-1 infection. We analyzed CD8+ T cells isolated from the blood of patients receiving anti-retroviral therapy (ART) within two weeks from the acute HIV-1 infection (EA, n=17) and patients, who initiated ART during chronic infection (LA, n=19). CD8+ T cells from the blood of age-matched non-infected individuals were used as a control (C, n=22). The phenotypic analysis evaluated the expression of b7, CCR5, CCR9 and CCR6 on naïve, central memory, effector memory and effector memory RA CD8+ T cells and related the expression of these molecules to whether the patients initiated ART during either acute or chronic HIV-1 infection. The expression of these markers was also analyzed after 5-day culture with IL-15 (20 ng/ml).

We found that the frequency of CCR6+ CD8+ T cells, especially central and effector memory subsets was reduced in HIV-1 infected patients independently of the time of ART initiation. Loss of expression of the CCR6 molecule on CD8+ T cells was associated with the elevated frequency of CD8+ T cells in blood of EA and LA patients. CCR6neg CD8+ T cells showed a senescent phenotype characterized by declined CD27/CD28 expression and poor degranulation capacity. In vitro incubation of CD8+ T cells from HIV-1 infected patients with IL-15 corrected the impaired phenotype of CD8+ T cells by restoring CCR6 and CD107a expression in CD8+ T cell subpopulations.

Our results show that lack of expression of CCR6 on CD8+ T cells is associated with an accumulation of CD8+ T cells in blood and that CCR6neg CD8+ T cells have an exhausted phenotype; these pathogenic features of HIV-1 infection are not corrected by early ART administration. IL-15 treatment reverts these abnormalities in vitro.

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