HIV Controllers Maintain a Population of Highly Efficient Th1 Effector Cells in Contrast to Patients Treated in the Long Term

Vingert, Benoît; Benati, Daniela; Lambotte, Olivier; Truchis, Pierre de; Slama, Laurence; Jeannin, Patricia; Galperin, Moran; Pérez-Patrigeón, Santiago; Boufassa, Faroudy; Kwok, William W.; Lemaı̂tre, Fabrice; Delfraissy, Jean‐François; Thèze, Jacques; Chakrabarti, Lisa A.

doi:10.1128/jvi.00056-12

Cited by 61 publications

(62 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although late-primed CD4 T cells provided help for B cells, they did not increase the level of endogenous preexisting LCMV-GP [33][34][35][36][37][38][39][40][41] tetramer + CD8 T cells by 8 d after transfer (in either undepleted or mice CD4 depleted before infection) and only induced a modest but unstained increase in cotransferred lateprimed virus-specific CD8 P14 T cells (Fig. 3C).…”

Section: Virus-specific Cd4 T Cells Primed In the Midst Of An Establimentioning

confidence: 92%

Type I interferon suppresses de novo virus-specific CD4 Th1 immunity during an established persistent viral infection

Osokine

Snell

Cunningham

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Significance Potent antiviral CD4 Th1 responses generated at the onset of persistent infection are lost as infection progresses. However, it is unknown how CD4 T cell responses are mounted in the midst of an established persistent infection to restore the diminishing Th1 response. We report that an established persistent virus infection suppresses the induction and distribution of new virus-specific CD4 Th1 cells. The failure to generate new Th1 responses is mediated by chronic type I interferon (IFN-I) signaling, and its blockade effectively restored de novo Th1 development. Our study identifies a mechanism of immunosuppression and a method to restore Th1 generation during persistent infection.

show abstract

Section: Virus-specific Cd4 T Cells Primed In the Midst Of An Establimentioning

confidence: 92%

Type I interferon suppresses de novo virus-specific CD4 Th1 immunity during an established persistent viral infection

Osokine

Snell

Cunningham

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Many other host and viral factors are potentially able to modify the efficacy of CD8 ϩ T-cell responses. For example, both CD4 ϩ and CD8 ϩ T cells from different individuals can vary in their abilities to target viral antigens (12,(24)(25)(26)(27)(28)(29)(30) and to exercise effector functions (31)(32)(33)(34). Similarly, differences in the replicative capacity of the transmitted virus (35,36) and differences due to virus-specific sequence variation in epitopes targeted by CTL (17,26) can modulate CD8 responses.…”

Section: T He Immune Response Mediated By Cytotoxic Cd8mentioning

confidence: 99%

Pressure from TRIM5α Contributes to Control of HIV-1 Replication by Individuals Expressing Protective HLA-B Alleles

Granier

Battivelli

Lécuroux

et al. 2013

J Virol

Self Cite

View full text Add to dashboard Cite

؉ patients who spontaneously controlled viral replication, but not viruses from viremic patients expressing these alleles, was significantly greater than that of viruses from patients not expressing these protective HLA-B alleles. Overall, a significant negative correlation between hTRIM5␣ sensitivity and viral load was observed. In HLA-B*57 ؉ patients, the T242N mutation in the HLA-B*57-restricted TW10 CD8 ؉ T lymphocyte (CTL) epitope was strongly associated with hTRIM5␣ sensitivity. In HLA-B*27 ؉ controllers, hTRIM5␣ sensitivity was associated with a significant reduction in emergence of key CTL mutations. In several patients, viral evolution to avoid hTRIM5␣ sensitivity was observed but could be associated with reduced viral replicative capacity. Thus, in individuals expressing protective HLA-B alleles, the combined pressures exerted by CTL, hTRIM5␣, and capsid structural constraints can prevent viral escape both by impeding the selection of necessary resistance/compensatory mutations and forcing the selection of escape mutations that increase hTRIM5␣ sensitivity or impair viral replicative capacity.

show abstract

“…Early studies attributed elite control to infection with less fit or defective viruses (16,17) while more recent studies describe ECs infected with virus with normal pathogenicity (18,19). Both CD4 ϩ and CD8 ϩ HIV-specific T cell responses are stronger in ECs than in subjects with progressive HIV infection (20)(21)(22). Some reports note that CD4 ϩ T cells from ECs are less susceptible to HIV infection (23,24), while others have found decreased virion production from HIV-infected cells in ECs (25) as well as decreased viral integration into the cellular genome (26).…”

mentioning

confidence: 99%

Cytokines Elevated in HIV Elite Controllers Reduce HIV ReplicationIn Vitroand Modulate HIV Restriction Factor Expression

Jacobs

Keating

Abdel‐Mohsen

et al. 2017

J Virol

View full text Add to dashboard Cite

A subset of HIV-infected individuals termed elite controllers (ECs) maintain CD4 ϩ T cell counts and control viral replication in the absence of antiretroviral therapy (ART). Systemic cytokine responses may differentiate ECs from subjects with uncontrolled viral replication or from those who require ART to suppress viral replication. We measured 87 cytokines in four groups of women: 73 ECs, 42 with pharmacologically suppressed viremia (ART), 42 with uncontrolled viral replication (noncontrollers [NCs]), and 48 HIV-uninfected (NEG) subjects. Four cytokines were elevated in ECs but not NCs or ART subjects: CCL14, CCL21, CCL27, and XCL1. In addition, median stromal cell-derived factor-1 (SDF-1) levels were 43% higher in ECs than in NCs. The combination of the five cytokines suppressed R5 and X4 virus replication in resting CD4 ϩ T cells, and individually SDF-1␤, CCL14, and CCL27 suppressed R5 virus replication, while SDF-1␤, CCL21, and CCL14 suppressed X4 virus replication. Functional studies revealed that the combination of the five cytokines upregulated CD69 and CCR5 and downregulated CXCR4 and CCR7 on CD4 ϩ T cells. The CD69 and CXCR4 effects were driven by SDF-1, while CCL21 downregulated CCR7. The combination of the EC-associated cytokines induced expression of the anti-HIV host restriction factors IFITM1 and IFITM2 and suppressed expression of RNase L and SAMHD1. These results identify a set of cytokines that are elevated in ECs and define their effects on cellular activation, HIV coreceptor expression, and innate restriction factor expression. This cytokine pattern may be a signature characteristic of HIV-1 elite control, potentially important for HIV therapeutic and curative strategies.IMPORTANCE Approximately 1% of people infected with HIV control virus replication without taking antiviral medications. These subjects, termed elite controllers (ECs), are known to have stronger immune responses targeting HIV than the typical HIV-infected subject, but the exact mechanisms of how their immune responses control infection are not known. In this study, we identified five soluble immune signaling molecules (cytokines) in the blood that were higher in ECs than in subjects with typical chronic HIV infection. We demonstrated that these cytokines can activate CD4 ϩ T cells, the target cells for HIV infection. Furthermore, these five EC-

show abstract

HIV Controllers Maintain a Population of Highly Efficient Th1 Effector Cells in Contrast to Patients Treated in the Long Term

Cited by 61 publications

References 85 publications

Type I interferon suppresses de novo virus-specific CD4 Th1 immunity during an established persistent viral infection

Type I interferon suppresses de novo virus-specific CD4 Th1 immunity during an established persistent viral infection

Pressure from TRIM5α Contributes to Control of HIV-1 Replication by Individuals Expressing Protective HLA-B Alleles

Cytokines Elevated in HIV Elite Controllers Reduce HIV ReplicationIn Vitroand Modulate HIV Restriction Factor Expression

Contact Info

Product

Resources

About