Distinctive Phenotype for HLA-E- Versus HLA-A2-restricted Memory CD8 αβT Cells in the Course of HCMV Infection Discloses Features Shared with NKG2CCD57NK and δ2γδT Cell Subsets

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2022 Dec 19

PMID 36532017

Authors

Amelie Rousseliere

Nathalie Gerard

Laurence Delbos

Pierrick Guerif

Magali Giral

Celine Bressollette-Bodin

Beatrice Charreau

Affiliations

Soon will be listed here.

Abstract

The human cytomegalovirus (HCMV) triggers both innate and adaptive immune responses, including protective CD8 αβT cells (CD8T) that contributes to the control of the infection. In addition to CD8T restricted by classical HLA class Ia molecules, HCMV also triggers CD8T recognizing peptides from the HCMV UL40 leader peptide and restricted by HLA-E molecules (HLA-E CD8T). This study investigated the frequency, phenotype and functions of HLA-E CD8T in comparison to the immunodominant HLA-A2 CD8T upon acute (primary or secondary infection) or chronic infection in kidney transplant recipients (KTR) and in seropositive (HCMV) healthy volunteer (HV) hosts. The frequency of hosts with detected HLA-E CD8T was similar after a primary infection (24%) and during viral latency in HCMV+ HV (26%) and equal to the frequency of HLA-A2 CD8T cells in both conditions (29%). Both CD8T subsets vary from 0.1% to >30% of total circulating CD8T according to the host. Both HLA-E and HLA-A2 CD8T display a phenotype specific of CD8 TEMRA (CD45RA/CCR7) but HLA-E CD8T express distinctive level for CD3, CD8 and CD45RA. Tim3, Lag-3, 4-1BB, and to a lesser extend 2B4 are hallmarks for T cell priming post-primary infection while KLRG1 and Tigit are markers for restimulated and long lived HCMV-specific CD8T responses. These cell markers are equally expressed on HLA-E and HLA-A2 CD8T. In contrast, CD56 and PD-1 are cell markers discriminating memory HLA-E- from HLA-A2-restricted CD8T. Long lived HLA-E display higher proliferation rate compared to HLA-A2 CD8T consistent with elevated CD57 expression. Finally, a comparative immunoprofiling indicated that HLA-E CD8T, divergent from HLA-A2 CD8T, share the expression of CD56, CD57, NKG2C, CD158 and the lack of PD-1 with NKG2CCD57+ NK and δ2γδT cells induced in response to HCMV and thus defines a common immunopattern for these subsets.

Citing Articles

Natural killer cell memory: challenges and opportunities for cancer immunotherapy.

Qu Y, Zeng A, Cheng Y, Li S Cancer Biol Ther. 2024; 25(1):2376410.

PMID: 38987282 PMC: 11238922. DOI: 10.1080/15384047.2024.2376410.

Identification a unique disulfidptosis classification regarding prognosis and immune landscapes in thyroid carcinoma and providing therapeutic strategies.

Feng Z, Zhao Q, Ding Y, Xu Y, Sun X, Chen Q J Cancer Res Clin Oncol. 2023; 149(13):11157-11170.

PMID: 37347261 DOI: 10.1007/s00432-023-05006-4.

Changes in HCMV immune cell frequency and phenotype are associated with chronic lung allograft dysfunction.

Rousseliere A, Delbos L, Foureau A, Reynaud-Gaubert M, Roux A, Demant X Front Immunol. 2023; 14:1143875.

PMID: 37187736 PMC: 10175754. DOI: 10.3389/fimmu.2023.1143875.

Persistent CD8 T Cell Marks Caused by the HCMV Infection in Seropositive Adults: Prevalence of HLA-E-Reactive CD8 T Cells.

Rousseliere A, Charreau B Cells. 2023; 12(6).

PMID: 36980230 PMC: 10047643. DOI: 10.3390/cells12060889.

References

Zhang N, Bevan M . CD8(+) T cells: foot soldiers of the immune system. Immunity. 2011; 35(2):161-8. PMC: 3303224. DOI: 10.1016/j.immuni.2011.07.010. View

Wherry E . T cell exhaustion. Nat Immunol. 2011; 12(6):492-9. DOI: 10.1038/ni.2035. View

Sylwester A, Nambiar K, Caserta S, Klenerman P, Picker L, Kern F . A new perspective of the structural complexity of HCMV-specific T-cell responses. Mech Ageing Dev. 2016; 158:14-22. DOI: 10.1016/j.mad.2016.03.002. View

Gabaev I, Steinbruck L, Pokoyski C, Pich A, Stanton R, Schwinzer R . The human cytomegalovirus UL11 protein interacts with the receptor tyrosine phosphatase CD45, resulting in functional paralysis of T cells. PLoS Pathog. 2011; 7(12):e1002432. PMC: 3234252. DOI: 10.1371/journal.ppat.1002432. View

Van Acker H, Capsomidis A, Smits E, Van Tendeloo V . CD56 in the Immune System: More Than a Marker for Cytotoxicity?. Front Immunol. 2017; 8:892. PMC: 5522883. DOI: 10.3389/fimmu.2017.00892. View

Sullivan L, Westall G, Widjaja J, Mifsud N, Nguyen T, Meehan A . The Presence of HLA-E-Restricted, CMV-Specific CD8+ T Cells in the Blood of Lung Transplant Recipients Correlates with Chronic Allograft Rejection. PLoS One. 2015; 10(8):e0135972. PMC: 4547726. DOI: 10.1371/journal.pone.0135972. View

El Hentati F, Gruy F, Iobagiu C, Lambert C . Variability of CD3 membrane expression and T cell activation capacity. Cytometry B Clin Cytom. 2009; 78(2):105-14. DOI: 10.1002/cyto.b.20496. View

Nicolas L, Monneret G, Debard A, Blesius A, Gutowski M, Salles G . Human gammadelta T cells express a higher TCR/CD3 complex density than alphabeta T cells. Clin Immunol. 2001; 98(3):358-63. DOI: 10.1006/clim.2000.4978. View

Lopez-Verges S, Milush J, Schwartz B, Pando M, Jarjoura J, York V . Expansion of a unique CD57⁺NKG2Chi natural killer cell subset during acute human cytomegalovirus infection. Proc Natl Acad Sci U S A. 2011; 108(36):14725-32. PMC: 3169160. DOI: 10.1073/pnas.1110900108. View

10.

Adland E, Klenerman P, Goulder P, Matthews P . Ongoing burden of disease and mortality from HIV/CMV coinfection in Africa in the antiretroviral therapy era. Front Microbiol. 2015; 6:1016. PMC: 4585099. DOI: 10.3389/fmicb.2015.01016. View

11.

Brenchley J, Karandikar N, Betts M, Ambrozak D, Hill B, Crotty L . Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells. Blood. 2002; 101(7):2711-20. DOI: 10.1182/blood-2002-07-2103. View

12.

Couzi L, Pitard V, Netzer S, Garrigue I, Lafon M, Moreau J . Common features of gammadelta T cells and CD8(+) alphabeta T cells responding to human cytomegalovirus infection in kidney transplant recipients. J Infect Dis. 2009; 200(9):1415-24. DOI: 10.1086/644509. View

13.

Ulbrecht M, Hofmeister V, Yuksekdag G, Ellwart J, Hengel H, Momburg F . HCMV glycoprotein US6 mediated inhibition of TAP does not affect HLA-E dependent protection of K-562 cells from NK cell lysis. Hum Immunol. 2003; 64(2):231-7. DOI: 10.1016/s0198-8859(02)00788-7. View

14.

Bressollette-Bodin C, Coste-Burel M, Besse B, Andre-Garnier E, Ferre V, Imbert-Marcille B . Cellular normalization of viral DNA loads on whole blood improves the clinical management of cytomegalovirus or Epstein Barr virus infections in the setting of pre-emptive therapy. J Med Virol. 2008; 81(1):90-8. DOI: 10.1002/jmv.21334. View

15.

Weekes M, Wills M, Mynard K, Hicks R, Sissons J, Carmichael A . Large clonal expansions of human virus-specific memory cytotoxic T lymphocytes within the CD57+ CD28- CD8+ T-cell population. Immunology. 1999; 98(3):443-9. PMC: 2326947. DOI: 10.1046/j.1365-2567.1999.00901.x. View

16.

Pietra G, Romagnani C, Mazzarino P, Falco M, Millo E, Moretta A . HLA-E-restricted recognition of cytomegalovirus-derived peptides by human CD8+ cytolytic T lymphocytes. Proc Natl Acad Sci U S A. 2003; 100(19):10896-901. PMC: 196899. DOI: 10.1073/pnas.1834449100. View

17.

Braud V, Allan D, OCallaghan C, Soderstrom K, DAndrea A, Ogg G . HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature. 1998; 391(6669):795-9. DOI: 10.1038/35869. View

18.

Gabanti E, Bruno F, Fornara C, Bernuzzi S, Lilleri D, Gerna G . Polyfunctional analysis of human cytomegalovirus (HCMV)-specific CD4(+) and CD8 (+) memory T-cells in HCMV-seropositive healthy subjects following different stimuli. J Clin Immunol. 2014; 34(8):999-1008. DOI: 10.1007/s10875-014-0093-5. View

19.

Holler P, Kranz D . Quantitative analysis of the contribution of TCR/pepMHC affinity and CD8 to T cell activation. Immunity. 2003; 18(2):255-64. DOI: 10.1016/s1074-7613(03)00019-0. View

20.

Baer A, Kehn-Hall K . Viral concentration determination through plaque assays: using traditional and novel overlay systems. J Vis Exp. 2014; (93):e52065. PMC: 4255882. DOI: 10.3791/52065. View