Neonatal mice possess two phenotypically and functionally distinct lung-migratory CD103+ dendritic cell populations following respiratory infection.

The CD103+ subset of lung-migratory dendritic cells (DCs) plays an important role in the generation of CD8+ T cell responses following respiratory infection. Here, we demonstrate that the dependence on CD103+ DCs for stimulation of RSV-specific T cells is both epitope and age-dependent. CD103+ DCs in neonatal mice develop two phenotypically and functionally distinct populations following respiratory infection. Neonatal CD103+ DCs expressing low levels of CD103 (CD103lo DCs) and other lineage and maturation markers including costimulatory molecules are phenotypically immature and functionally limited. CD103lo DCs sorted from infected neonates were unable to stimulate cells of the KdM282-90 specificity, which are potently stimulated by CD103hi DCs sorted from the same animals. These data suggest that the delayed maturation of CD103+ DCs in the neonate limits the KdM282-90-specific response and explain the distinct CD8+ T cell response hierarchy displayed in neonatal mice that differs from the hierarchy seen in adult mice. These findings have implications for the development of early-life vaccines, where the promotion of responses with less age bias may prove advantageous. Alternately, specific approaches may be used to enhance the maturation and function of the CD103lo DC population in neonates to promote more adult-like T cell responses.

In vitro stimulation with a non-peptidic alkylphosphate expands cells expressing Vgamma2-Jgamma1.2/Vdelta2 T-cell receptors.

The majority of peripheral blood gammadelta T cells in healthy adult humans express the Vgamma2/Vdelta2 T-cell receptor (TCR) and generate TCR-mediated, major histocompatibility complex (MHC)-unrestricted proliferative responses to low molecular weight alkylphosphates. Vgamma2/Vdelta2 populations after antigen proliferation maintained diversity in the CDR3s of Vgamma2 mRNA, indicating that the response was polyclonal or oligoclonal, and were enriched for Vgamma2 TCR chains containing the Jgamma1.2 segment. Alkylphosphate stimulation further skewed an already biased peripheral blood gammadelta T-cell population and increased the abundance of Vgamma2-Jgamma1.2/Vdelta2 T cell receptors, suggesting similarities between the alkylphosphate response and peripheral selection mechanisms shaping this repertoire in human beings.

Vaccination with tat toxoid attenuates disease in simian/HIV-challenged macaques.

The Tat protein is essential for HIV type 1 (HIV-1) replication and may be an important virulence factor in vivo. We studied the role of Tat in viral pathogenesis by immunizing rhesus macaques with chemically inactivated Tat toxoid and challenging these animals by intrarectal inoculation with the simian/human immunodeficiency virus 89.6PD. Immune animals had significantly attenuated disease with lowered viral RNA, interferon-alpha, and chemokine receptor expression (CXCR4 and CCR5) on CD4(+) T cells; these features of infection have been linked to in vitro effects of Tat and respond similarly to extracellular Tat protein produced during infection. Immunization with Tat toxoid inhibits key steps in viral pathogenesis and should be included in therapeutic or preventive HIV-1 vaccines.