Impact of maternal engrafted cytomegalovirus‐specific CD8+ T cells in a patient with severe combined immunodeficiency. Issue 4 (13th April 2021)

• Record Type: Journal Article
• Authors: Koh, June‐Young; Lee, Sang‐Bo; Kim, Borahm; Park, Younhee; Choi, Jong Rak; Son, Sohee; Kim, Yae‐Jean; Hahn, Seung Min; Ahn, Jong Gyun; Kang, Ji‐Man; Shin, Eui‐Cheol
• Is Part Of: Clinical & translational immunology. Volume 10:Issue 4(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-04-13
• Subjects: severe combined immunodeficiency -- transplacental maternal engraftment -- CD8+ T cells -- cytomegalovirus infection -- haploidentical haematopoietic stem cell transplantation; Immunologic diseases -- Periodicals; Immunology -- Periodicals; Clinical medicine -- Periodicals; Immune System Diseases -- therapy; Immunotherapy; Immunologic Factors -- therapeutic use; Translational Medical Research; Molecular Targeted Therapy; Clinical medicine; Immunologic diseases; Immunology; Periodicals; Periodicals; Fulltext; Internet Resources; Periodicals; 616.079
• DOI: 10.1002/cti2.1272
• Languages: English
• ISSNs: 2050-0068

Abstract

Abstract: Objectives: In patients with severe combined immunodeficiency (SCID), the immune system often fails to eradicate maternal cells that enter the foetus via the placenta, resulting in transplacental maternal engraftment (TME) syndrome. However, the clinical significance of TME has not been comprehensively elucidated. Methods: Here, we describe a patient with SCID with a novel frameshift IL2RG mutation associated with maternal engrafted CD8 + T cells that had been expanded by viral infection. To evaluate the origin of the expanded T cells, we HLA‐typed the myeloid and T cells of the patient and analysed the immunological characteristics of the expanded CD8 + T cells using T‐cell receptor (TCR) repertoire and flow cytometry analysis. Results: In our patient, the maternal engrafted CD8 + T cells expanded and exerted in vitro antiviral function against human cytomegalovirus (CMV) infection before and after haematopoietic cell transplantation (HCT). After haploidentical HCT from the maternal donor, maternal engrafted CMV‐specific CD8 + T cells were maintained, successfully proliferated and activated against CMV. We found no evidence of acute graft‐versus‐host disease or infectious complications other than recurrent episodes of CMV viraemia, which were well controlled by ganciclovir and, possibly by, the maternal engrafted CMV‐specific CD8 + T cells. Conclusion: Our findings elucidate a possible functional role of TME in controlling CMV infection in patient with SCID and suggest an optimal strategy for donor selection in patients with SCID with TME. Abstract : We describe a patient with severe combined immunodeficiency (SCID) with a novel frameshift IL2RG mutation associated with maternal engrafted CD8 + T cells that expanded and exerted antiviral function against human cytomegalovirus (CMV) infection.