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

par Marchant, Arnaud ;Appay, Victor;van der Sande, Marianne;Dulphy, Nicolas;Liesnard, Corinne ;Kidd, Michael;Kaye, Steve;Ojuola, Olubukola;Gillespie, Geraldine M A;Vargas Cuero, Ana L;Cerundolo, V;Callan, Margaret;McAdam, K P;Rowland-Jones, Sarah;donner, catherine ;McMichael, Andrew J;Whittle, Hilton
Référence The Journal of clinical investigation, 111, 11, page (1747-1755)
Publication Publié, 2003-06

Article révisé par les pairs

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Résumé :

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(+), perforin(low)), and they acquired a late differentiation phenotype (CD28(-)CD27(-)CD45RA(+), perforin(high)) 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.