Inhibitory Potential of Subpopulations of CD8 + T Cells in HIV-1-Infected Elite Suppressors

Self Cite

Section: A) C)contrasting

confidence: 56%

Section: Resultsmentioning

confidence: 99%

Comparative Analysis of the Capacity of Elite Suppressor CD4 ⁺ and CD8 ⁺ T Cells To Inhibit HIV-1 Replication in Monocyte-Derived Macrophages

Walker-Sperling

Buckheit

Blankson

2014

Self Cite

“…The high cytotoxic potential of HIV-specific CD8 ϩ T cells has also been reported by others after in vitro culture with HIV antigens (15,48,49). However, our first report described only 11 subjects, the majority of whom expressed HLA-B*57 or HLA-B*27 or both.…”

Section: Discussionmentioning

confidence: 53%

Both HLA-B*57 and Plasma HIV RNA Levels Contribute to the HIV-Specific CD8 ⁺ T Cell Response in HIV Controllers

Lécuroux

Sáez‐Cirión

Girault

et al. 2014

g CD8؉ T cell responses are thought to play an important role during HIV infection, particularly in HIV controllers (HIC) in whom viral replication is spontaneously controlled without any treatment. We have demonstrated that CD8 ؉ T cells from these subjects are able to suppress viral replication in vitro. In parallel, HIV-specific CD8 ؉ responses were shown to be strong and of high quality, with proliferative abilities and cytotoxic capacities, in HIC. The HLA-B*57 allele, which is associated with a better clinical outcome in HIV infection, is overrepresented in HIC. However, we showed that these patients constitute a heterogeneous group that includes subjects who present weak suppression of viral replication in vitro and HIV-specific responses. We performed an extensive study of 101 HIC (49 HLA-B*57؉ and 52 HLA-B*57 ؊ ) to determine the impact of HLA-B*57 on the HIVspecific CD8؉ response. The HLA-B*57-restricted response displayed better qualitative features, such as higher functional avidity, higher proliferation capacity, and a higher level of cytokine production, than responses not restricted by HLA-B*57. However, the highest frequencies of HIV-specific CD8 ؉ T cells were observed only in a subset of HLA-B*57 ؉ subjects. They were tightly associated with the ability to suppress viral replication in vitro. In contrast, the subset of HLA-B*57؉ subjects with a weak ability to suppress viral replication had significantly lower ultrasensitive viral loads than all the other groups of controllers. In conclusion, both HLA-B*57 and the amount of ultrasensitive viral load seem to play a role in HIV-specific CD8 ؉ T cell responses in HIC.

“…Accordingly, Buckheit et al have previously demonstrated that HIV-specific CD8 ϩ T cell subsets exhibit different in vitro suppressive activities depending on the time point considered: terminally differentiated cells were more suppressive at an early stage, whereas a less differentiated fraction exhibited an equally suppressive function at later time points (33). Polyfunctionality, a marker of efficient T cell responses, may thus also rely on the diversity of CD8 ϩ T cell differentiation ensuring a large timescale of cytotoxic responses balancing from immediate to late induced cytotoxic activity.…”

Section: Previous Reports Have Suggested That Hiv-specific Cd8mentioning

confidence: 99%

High Eomesodermin Expression among CD57 ⁺ CD8 ⁺ T Cells Identifies a CD8 ⁺ T Cell Subset Associated with Viral Control during Chronic Human Immunodeficiency Virus Infection

Simonetta

Hua

Lécuroux

et al. 2014

During HIV infection, increased CD57 expression among CD8؉ T cells has been associated with immune senescence and defective immune responses. Interestingly, CD57-expressing CD8؉ T cells exhibit a dual profile, being simultaneously highly cytotoxic (terminally differentiated effectors) and poorly proliferative (replicative senescent). Recent publications point toward a positive role of CD57-expressing CD8 ؉ T cell subsets, presumably due to their high cytolytic activity. We further investigated the phenotype of CD57-expressing CD8 ؉ T cells in healthy donors and during HIV infection combining CD57 expression to Eomesodermin (EOMES), a T box transcription factor which determines, coordinately with T-bet, effector and memory CD8 ؉ T cell differentiation. We defined in healthy donors two functionally distinct CD57-expressing CD8 primary infected patients, long-term viremic patients, aviremic patients treated with antiretroviral therapy, and HIV controllers; we demonstrated a higher percentage of CD57-expressing cells in all HIV-infected patients regardless of virological status. When heterogeneity in EOMES expression among CD57 cells was taken into account, we detected significantly higher proportions of EOMES hi CD57؉ cells among HIV-specific and nonspecific CD8 ؉ T cells from HIV controllers than in aviremic antiretroviral-treated patients and viremic patients. Importantly, such a peculiar non-terminally differentiated EOMES hi CD57 ؉ phenotypic profile was associated with viral control. IMPORTANCEThis study demonstrates that functional heterogeneity exists among CD57-expressing CD8 T cells, which include both terminally differentiated, highly cytotoxic EOMES int CD57 ؉ CD8 ؉ T cells and less differentiated EOMES hi CD57 ؉ CD8 T cells, which do not exhibit immediate cytotoxic functions but present high proliferative capacity. Interestingly, HIV controllers present a high proportion of EOMES hi CD57 cells among CD57-expressing HIV-specific CD8 T cells compared to both long-term viremic and aviremic antiretroviral therapy (ART)-treated patients, suggesting a beneficial role for this cell subset in viral control.