Acute neonatal infections 'lock-in' a suboptimal CD8+ T cell repertoire with impaired recall responses.
Microbial infection during various stages of human development produces widely different clinical outcomes, yet the links between age-related changes in the immune compartment and functional immunity remain unclear. The ability of the immune system to respond to specific antigens and mediate protection in early life is closely correlated with the level of diversification of lymphocyte antigen receptors. We have previously shown that the neonatal primary CD8+ T cell response to replication competent virus is significantly constricted compared to the adult response. In the present study, we have analyzed the subsequent formation of neonatal memory CD8+ T cells and their response to secondary infectious challenge. In particular, we asked whether the less diverse CD8+ T cell clonotypes that are elicited by neonatal vaccination with replication competent virus are 'locked-in' to the adult memory T cell, and thus may compromise the strength of adult immunity. Here we report that neonatal memory CD8+ T cells mediate poor recall responses compared to adults and are comprised of a repertoire of lower avidity T cells. During a later infectious challenge the neonatal memory CD8+ T cells compete poorly with the fully diverse repertoire of naïve adult CD8+ T cells and are outgrown by the adult primary response. This has important implications for the timing of vaccination in early life.
Department of Microbiology and Immunology, Cornell University, Ithaca, New York, United States of America.
Brian D
BD
Rudd
Vanessa
V
Venturi
Norah L
NL
Smith
Kito
K
Nzingha
Emily L
EL
Goldberg
Gang
G
Li
Janko
J
Nikolich-Zugich
Miles P
MP
Davenport
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004274:DNA, Recombinant / Q000378:metabolism; D006561:Herpes Simplex / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007107:Immune System / Q000254:growth & development / Q000276:immunology / Q000473:pathology; D007153:Immunologic Deficiency Syndromes / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007156:Immunologic Memory; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity; D008088:Listeriosis / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology* / Q000517:prevention & control; D008815:Mice, Inbred Strains; D018448:Models, Immunological; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000276:immunology*; D014615:Vaccinia / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014774:Virulence
D004274:DNA, Recombinant; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014613:Vaccines, Attenuated