Mature CD8+ T lymphocyte response to viral infection during fetal life
Arnaud Marchant, Victor Appay, Marianne van der Sande, Nicolas Dulphy, Corinne Liesnard, Michael Kidd, Steve Kaye, Olubukola Ojuola, Geraldine M.A. Gillespie, Ana L. Vargas Cuero, Vincenzo Cerundolo, Margaret Callan, Keith P.W.J. McAdam, Sarah L. Rowland-Jones, Catherine Donner, Andrew J. McMichael, Hilton Whittle
Arnaud Marchant, Victor Appay, Marianne van der Sande, Nicolas Dulphy, Corinne Liesnard, Michael Kidd, Steve Kaye, Olubukola Ojuola, Geraldine M.A. Gillespie, Ana L. Vargas Cuero, Vincenzo Cerundolo, Margaret Callan, Keith P.W.J. McAdam, Sarah L. Rowland-Jones, Catherine Donner, Andrew J. McMichael, Hilton Whittle
View: Text | PDF
Article

Mature CD8+ T lymphocyte response to viral infection during fetal life

Abstract

Immunization of newborns against viral infections may be hampered by ineffective CD8+ T cell responses. To characterize the function of CD8+ T lymphocytes in early life, we studied newborns with congenital human cytomegalovirus (HCMV) infection. We demonstrate that HCMV infection in utero leads to the expansion and the differentiation of mature HCMV-specific CD8+ T cells, which have similar characteristics to those detected in adults. High frequencies of HCMV-specific CD8+ T cells were detected by ex vivo tetramer staining as early as after 28 weeks of gestation. During the acute phase of infection, these cells had an early differentiation phenotype (CD28–CD27+CD45RO+, perforinlow), and they acquired a late differentiation phenotype (CD28–CD27-CD45RA+, perforinhigh) during the course of the infection. The differentiated cells showed potent perforin-dependent cytolytic activity and produced antiviral cytokines. The finding of a mature and functional CD8+ T cell response to HCMV suggests that the machinery required to prime such responses is in place during fetal life and could be used to immunize newborns against viral pathogens.

Authors

Arnaud Marchant, Victor Appay, Marianne van der Sande, Nicolas Dulphy, Corinne Liesnard, Michael Kidd, Steve Kaye, Olubukola Ojuola, Geraldine M.A. Gillespie, Ana L. Vargas Cuero, Vincenzo Cerundolo, Margaret Callan, Keith P.W.J. McAdam, Sarah L. Rowland-Jones, Catherine Donner, Andrew J. McMichael, Hilton Whittle

×

Figure 2

Options: View larger image (or click on image) Download as PowerPoint
TCR BV spectratypic analysis of CD8+ T lymphocytes and phenotypic analys...
TCR BV spectratypic analysis of CD8+ T lymphocytes and phenotypic analysis of BV-specific CD8+ T cells from control and HCMV-infected newborns. (a) Spectratypic analysis. CDR3 length distribution was Gaussian for all BV families of control newborn no. 9 (shows five representative families), indicating a naive CD8+ T cell repertoire. Similar results were obtained in control newborns no. 8 and 12. In contrast, alterations in CDR3 length distribution were detected in BV16, BV18, and BV23 of case no. 7, indicating oligoclonal expansions of CD8+ T cells. (b and c) Phenotypic analysis. Expression of HLA-DR, CD27, and CD28 by BV2, BV14, BV16, BV18, and BV23 CD8+ T cells of control no. 9 and case no. 7. High proportions of CD8+ T lymphocytes from HCMV-infected newborns had a phenotype of activated (b) and differentiated (c) cells. These alterations were primarily observed in the BV families that included oligoclonal expansions in the spectratypic analysis (BV16, BV18, and BV23).