Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Feb 6:65:e14.
doi: 10.1590/S1678-9946202365014. eCollection 2023.

Expression of TIGIT, PD-1 and HLA-DR/CD38 markers on CD8-T cells of children and adolescents infected with HIV and uninfected controls

Wânia Ferraz Pereira-Manfro  1 , Giselle Pereira da Silva  1 , Priscilla Ramos Costa  2 , Dayane Alves Costa  2 , Bianca da Silva Ferreira  3 , Daniela Mena Barreto  3 , Ana Cristina Cisne Frota  3 , Cristina Barroso Hofer  3   4 , Esper Georges Kallas  2 , Lucimar Gonçalves Milagres  1
Affiliations

Expression of TIGIT, PD-1 and HLA-DR/CD38 markers on CD8-T cells of children and adolescents infected with HIV and uninfected controls

Wânia Ferraz Pereira-Manfro et al. Rev Inst Med Trop Sao Paulo. .

Abstract

Immune exhaustion and senescence are scarcely studied in HIV-pediatric patients. We studied the circulatory CD8 T cells activation/exhaustion and senescent phenotype of children and adolescents vertically infected with HIV or uninfected controls based on the expression of human leukocyte antigen (HLA-DR), CD38, T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), programmed death 1 (PD-1) and CD57 by flow cytometry, during approximately one year. Eleven HIV-infected (HI) and nine HIV-uninfected (HU) children/adolescents who received two doses or one dose of meningococcal C conjugate vaccine (MenC), respectively, were involved in this study. Blood samples were collected before the immunization (T0), 1-2 months after the first dose (T1), and 1-2 months after the second dose (T2), which was administered approximately one year after the first one. HI patients not receiving combined antiretroviral therapy (cART) showed a higher frequency of CD8 T cells TIGIT+, PD-1+ or CD57+, as well as a higher frequency of CD8 T cells co-expressing CD38/HLA-DR/TIGIT or CD38/HLA-DR/PD-1 when compared to HI treated or HU individuals, at all times that they were assessed. CD8 T cells co-expressing CD38/DR/TIGIT were inversely correlated with the CD4/CD8 ratio but positively associated with viral load. The co-expression of CD38/DR/TIGIT or CD38/DR/PD-1 on CD8 T cells was also inversely associated with the CD4 T cells expressing co-stimulatory molecules CD127/CD28. The results showed a higher expression of exhaustion/senescence markers on CD8 T cells of untreated HI children/adolescents and its correlations with viral load.

PubMed Disclaimer

Conflict of interest statement

CONFLICT OF INTERESTS

The authors declare no conflict of interests.

Figures

Figure 1
Figure 1. Increased expression of activation, exhaustion, and senescent markers on CD8-T cells from HIV-untreated patients. Blood samples were collected before immunization (T0), 1–2 months after the first dose (T1), and 1–2 months after a booster dose of MenC (T2) (A). Frequency of CD8+ T cells expressing (B) TIGIT, (C) PD-1, (D) co-expressing PD-1-TIGIT, (E) CD38-DR, (F) CD38-DR-PD-1, (G) CD38-DR-TIGIT, (H) CD57+CD28– at different time-points. P-values were calculated using the Mann-Whitney’s test. p< 0.05 was taken as significant. cART = combined antiretroviral therapy; HI = HIV infected; HU = HIV uninfected; MenC = meningococcal C conjugate vaccine.
Figure 2
Figure 2. Strategy of flow cytometry’s analysis from one representative experiment with PBMC samples of an HIV-infected patient: (A) Different parameters were chosen first: Time x PE to check laser status; Singlets to exclude the cell doublets; Live/Dead x CD3 to select living cells expressing CD3; and Gate CD8xCD4 to choose CD8+ T cells; (B) Cellular activation was characterized through the expression of HLA-DR and CD38; (C) Cellular exhaustion and senescence were characterized by the expression of PD-1, TIGIT and CD57; (D) Co-expression of activation and inhibitory markers was done by first gating TIGIT or PD-1 CD8+ T cells, and afterwards gating cells positive for CD38 and HLA-DR.
Figure 3
Figure 3. CD8+ T cells expressing CD38-DR-TIGIT or PD-1 inversely correlated with CD4/CD8 ratio and CD4 T cells expressing stimulatory molecules. Associations of CD8 and CD4 T cells exhausted profile. CD8+ T cells expressing CD38-DR-TIGIT negatively correlated with CD4/CD8 ratio (A) and were positively associated with viral load (B). Positive correlation of CD8 T cells CD38+DR+TIGIT+ with CD4 T cells CD38+DR+TIGIT+ at T0 (C) and T1 (D). CD8 T cells expressing CD38-DR-TIGIT (E) or PD-1 (F) inversely correlated with CD4+ T cells CD127+CD28+. Spearman’s non-parametric test was used for correlation analyses. p< 0.05 was taken as significant.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Perdomo-Celis F, Velilla PA, Taborda NA, Rugeles MT. An altered cytotoxic program of CD8+ T-cells in HIV-infected patients despite HAART-induced viral suppression. PLoS One. 2019;14:e0210540. - PMC - PubMed
    1. Chen H, Moussa M, Catalfamo M. The role of immunomodulatory receptors in the pathogenesis of HIV infection: a therapeutic opportunity for HIV cure? Front Immunol. 2020;11:1223–1223. - PMC - PubMed
    1. Deeks SG, Verdin E, McCune JM. Immunosenescence and HIV. Curr Opin Immunol. 2012;24:501–506. - PubMed
    1. Paris RM, Milagres LG, Moysi E, Okulicz JF, Agan BK, Ganesan A, et al. Lower baseline germinal center activity and preserved Th1 immunity are associated with Hepatitis B vaccine response in treated HIV infection. Pathog Immun. 2017;2:66–88. - PMC - PubMed
    1. Ndhlovu ZM, Kamya P, Mewalal N, Kløverpris HN, Nkosi T, Pretorius K, et al. Magnitude and kinetics of CD8+ T cell activation during hyperacute HIV infection impact viral set point. Immunity. 2015;43:591–604. - PMC - PubMed