Acute Neonatal Infections ‘Lock-In’ a Suboptimal CD8+ T Cell Repertoire with Impaired Recall Responses

• DOI: 10.1371/journal.ppat.1003572
• Publication Date: 2013-09-12T21:06:09Z
• Authors: Brian D. Rudd; Vanessa Venturi; Norah L. Smith; Kito Nzingha; Emily L. Goldberg; Gang Li; Janko Nikolich-Zu...; Miles P. Davenport
• Keywords: 0301 basic medicine; Aging; Receptors, Antigen, T-Cell, alpha-beta; 3207 Medical Microbiology; Inbred Strains; 32 Biomedical and Clinical Sciences; Herpesvirus 1, Human; CD8-Positive T-Lymphocytes; Mice; Models; Receptors; Vaccinia; 2.1 Biological and endogenous factors; Listeriosis; anzsrc-for: 1107 Immunology; Biology (General); anzsrc-for: 3204 Immunology; Pediatric; alpha-beta; Vaccines; Recombinant; Virulence; 3 Good Health and Well Being; anzsrc-for: 3107 Microbiology; Specific Pathogen-Free Organisms; 3. Good health; 3204 Immunology; Infectious Diseases; Immunological; Antigen; Human; Research Article; anzsrc-for: 1108 Medical Microbiology; 570; QH301-705.5; 1.1 Normal biological development and functioning; DNA, Recombinant; 610; Mice, Inbred Strains; Vaccinia virus; Vaccines, Attenuated; Vaccine Related; 03 medical and health sciences; anzsrc-for: 32 Biomedical and Clinical Sciences; Biodefense; Animals; anzsrc-for: 3207 Medical Microbiology; Herpesvirus 1; Inflammatory and immune system; Immunologic Deficiency Syndromes; Models, Immunological; Herpes Simplex; DNA; RC581-607; Newborn; T-Cell; Listeria monocytogenes; Emerging Infectious Diseases; Attenuated; anzsrc-for: 0605 Microbiology; Animals, Newborn; Immune System; Immunization; Immunologic diseases. Allergy; Immunologic Memory

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.