The BTLA-HVEM-CD5 Immunoregulatory Axis-An Instructive Mechanism Governing pTreg Cell Differentiation

doi:10.3389/fimmu.2019.01163

Review

. 2019 May 22:10:1163.

doi: 10.3389/fimmu.2019.01163. eCollection 2019.

The BTLA-HVEM-CD5 Immunoregulatory Axis-An Instructive Mechanism Governing pTreg Cell Differentiation

Jessica Bourque¹, Daniel Hawiger¹

Affiliations

PMID: 31191536
PMCID: PMC6541033
DOI: 10.3389/fimmu.2019.01163

Review

The BTLA-HVEM-CD5 Immunoregulatory Axis-An Instructive Mechanism Governing pTreg Cell Differentiation

Jessica Bourque et al. Front Immunol. 2019.

. 2019 May 22:10:1163.

doi: 10.3389/fimmu.2019.01163. eCollection 2019.

Authors

Jessica Bourque¹, Daniel Hawiger¹

Affiliation

¹ Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, United States.

PMID: 31191536
PMCID: PMC6541033
DOI: 10.3389/fimmu.2019.01163

No abstract available

Keywords: BTLA; CD5; HVEM; dendritic cells; pTreg cells.

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Figures

**Figure 1**
Some cDC1s express BTLA, which can signal through HVEM in naïve CD4⁺ T cells to activate MEK and subsequently ETS1 to increase expression of *Cd5*. High CD5 expression allows these to cells to convert to Foxp3⁺ pTreg cells by interfering with mTOR activation, even in the presence of effector-differentiating cytokines such as IL-4, IL-6, and IFN-γ.

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References

1. Soldevila G, Raman C, Lozano F. The immunomodulatory properties of the CD5 lymphocyte receptor in health and disease. Curr Opin Immunol. (2011) 23:310–8. 10.1016/j.coi.2011.03.003 - DOI - PMC - PubMed
1. Azzam HS, Grinberg A, Lui K, Shen H, Shores EW, Love PE. CD5 expression is developmentally regulated by T cell receptor (TCR) signals and TCR avidity. J Exp Med. (1998) 188:2301–11. 10.1084/jem.188.12.2301 - DOI - PMC - PubMed
1. Axtell RC, Xu L, Barnum SR, Raman C. CD5-CK2 binding/activation-deficient mice are resistant to experimental autoimmune encephalomyelitis: protection is associated with diminished populations of IL-17-expressing T cells in the central nervous system. J Immunol. (2006) 177:8542–9. 10.4049/jimmunol.177.12.8542 - DOI - PMC - PubMed
1. Gary-Gouy H, Lang V, Sarun S, Boumsell L, Bismuth G. In vivo association of CD5 with tyrosine-phosphorylated ZAP-70 and p21 phospho-zeta molecules in human CD3+ thymocytes. J Immunol. (1997) 159:3739–47. - PubMed
1. Mier-Aguilar CA, Vega-Baray B, Burgueno-Bucio E, Lozano F, Garcia-Zepeda EA, Raman C, et al. . Functional requirement of tyrosine residue 429 within CD5 cytoplasmic domain for regulation of T cell activation and survival. Biochem Biophys Res Commun. (2015) 466:381–7. 10.1016/j.bbrc.2015.09.033 - DOI - PubMed

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[1] Soldevila G, Raman C, Lozano F. The immunomodulatory properties of the CD5 lymphocyte receptor in health and disease. Curr Opin Immunol. (2011) 23:310–8. 10.1016/j.coi.2011.03.003 - DOI - PMC - PubMed

[2] Soldevila G, Raman C, Lozano F. The immunomodulatory properties of the CD5 lymphocyte receptor in health and disease. Curr Opin Immunol. (2011) 23:310–8. 10.1016/j.coi.2011.03.003 - DOI - PMC - PubMed

[3] Azzam HS, Grinberg A, Lui K, Shen H, Shores EW, Love PE. CD5 expression is developmentally regulated by T cell receptor (TCR) signals and TCR avidity. J Exp Med. (1998) 188:2301–11. 10.1084/jem.188.12.2301 - DOI - PMC - PubMed

[4] Azzam HS, Grinberg A, Lui K, Shen H, Shores EW, Love PE. CD5 expression is developmentally regulated by T cell receptor (TCR) signals and TCR avidity. J Exp Med. (1998) 188:2301–11. 10.1084/jem.188.12.2301 - DOI - PMC - PubMed

[5] Axtell RC, Xu L, Barnum SR, Raman C. CD5-CK2 binding/activation-deficient mice are resistant to experimental autoimmune encephalomyelitis: protection is associated with diminished populations of IL-17-expressing T cells in the central nervous system. J Immunol. (2006) 177:8542–9. 10.4049/jimmunol.177.12.8542 - DOI - PMC - PubMed

[6] Axtell RC, Xu L, Barnum SR, Raman C. CD5-CK2 binding/activation-deficient mice are resistant to experimental autoimmune encephalomyelitis: protection is associated with diminished populations of IL-17-expressing T cells in the central nervous system. J Immunol. (2006) 177:8542–9. 10.4049/jimmunol.177.12.8542 - DOI - PMC - PubMed

[7] Gary-Gouy H, Lang V, Sarun S, Boumsell L, Bismuth G. In vivo association of CD5 with tyrosine-phosphorylated ZAP-70 and p21 phospho-zeta molecules in human CD3+ thymocytes. J Immunol. (1997) 159:3739–47. - PubMed

[8] Gary-Gouy H, Lang V, Sarun S, Boumsell L, Bismuth G. In vivo association of CD5 with tyrosine-phosphorylated ZAP-70 and p21 phospho-zeta molecules in human CD3+ thymocytes. J Immunol. (1997) 159:3739–47. - PubMed

[9] Mier-Aguilar CA, Vega-Baray B, Burgueno-Bucio E, Lozano F, Garcia-Zepeda EA, Raman C, et al. . Functional requirement of tyrosine residue 429 within CD5 cytoplasmic domain for regulation of T cell activation and survival. Biochem Biophys Res Commun. (2015) 466:381–7. 10.1016/j.bbrc.2015.09.033 - DOI - PubMed

[10] Mier-Aguilar CA, Vega-Baray B, Burgueno-Bucio E, Lozano F, Garcia-Zepeda EA, Raman C, et al. . Functional requirement of tyrosine residue 429 within CD5 cytoplasmic domain for regulation of T cell activation and survival. Biochem Biophys Res Commun. (2015) 466:381–7. 10.1016/j.bbrc.2015.09.033 - DOI - PubMed

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The BTLA-HVEM-CD5 Immunoregulatory Axis-An Instructive Mechanism Governing pTreg Cell Differentiation

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The BTLA-HVEM-CD5 Immunoregulatory Axis-An Instructive Mechanism Governing pTreg Cell Differentiation

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