S of expression of important pneumococcal genes, including vaccine candidates, in the human nasopharynx and have established the basis for future gene expression studies during human pneumococcal disease.AcknowledgmentsWe are grateful to Dr. Lesley McGee from CDC for providing all normal flora strains. The authors also thank Dr. Daiichi Morii, Magderie Klugman, Paulina Hawkins and Dr. Sopio Chochua for their invaluable assistance in some molecular reactions. We appreciate the help of Gideon Matzkin for critical reading of the manuscript. Investigators Group: Vanderbilt University: Dr. Carlos G. Grijalva, Dr. Kathryn M. Edwards, Dr. John V. Williams, and Dr. Marie R. Griffin; and the Instituto de Investigacion Nutricional, Lima, Peru: Hector ?Verastegui, Ana I. Gil, and Dr. Claudio F. Lanata.Author ContributionsConceived and designed the experiments: KPK JEV. Performed the experiments: FS SJT JEV. get AKT inhibitor 2 Analyzed the data: FS KPK JEV. Wrote the paper: FS JEV.
Following acute viral or bacterial infection, antigen-specific T cells clonally expand and acquire effector functions that contribute to pathogen clearance. The expansion phase is robust, represent?ing as much as a 50,000?00,000-fold increase from the naive precursor frequency. Following elimination of the pathogen, 90?95 of effector T cells die, leaving behind a long-lived pool of memory T cells. These memory T cells provide protection to subsequent infections with the same or similar pathogens [1]. A major focus of recent study is to determine the molecular signals that control the memory fate decision allowing a minority of effector T cells to survive into the memory pool. CD4+ T cell responses to acute viral or intracellular bacterial infection differ from CD8+ T cell responses with respect to their requirement for TCR-driven differentiation signals. For example, CD8+ T cells require only a short period of antigenic stimulation (6?4 hours) to drive recruitment and programmed differentiation [2?]. CD4+ T cells, on the other hand, require several days of in vivo antigen exposure to achieve maximal expansion and differentiation into pathogen-specific effector cells [6?]. These observations K162 supplier suggest that CD4+ T cells translate TCR signals into a downstream activation/differentiation program in a fundamentally different fashion than do CD8+ T cells. Additionally, the requirement for prolonged exposure to antigen suggests that CD4+ T cell differentiation and survival may be prone to selection on the basis of qualitative and/or quantitative components of the antigen signal [9?1]. One insight into these potential differences between CD4+ and CD8+ T cells came from the observation that CD8+ T cell repertoires are unchanged after the effector phase. For CD8+ T cells, there is no difference in the frequency of distribution ofindividual clonal populations within a pool of cells with a given specificity when comparing effector, memory or secondary effector populations [12]. Conversely, CD4+ T cell repertoires undergo antigen-driven revision and skewing during successive antigen challenges [9,13]. However, one important issue unresolved by these prior studies is how the differentiation and survival of effector cells during the transition into the Th1 memory pool is dependent upon TCR-mediated signals delivered during the primary response, including the amount and duration of antigen, structural avidity of the TCR, the type and maturation state of the antigen presenting cell, and the inflammatory envi.S of expression of important pneumococcal genes, including vaccine candidates, in the human nasopharynx and have established the basis for future gene expression studies during human pneumococcal disease.AcknowledgmentsWe are grateful to Dr. Lesley McGee from CDC for providing all normal flora strains. The authors also thank Dr. Daiichi Morii, Magderie Klugman, Paulina Hawkins and Dr. Sopio Chochua for their invaluable assistance in some molecular reactions. We appreciate the help of Gideon Matzkin for critical reading of the manuscript. Investigators Group: Vanderbilt University: Dr. Carlos G. Grijalva, Dr. Kathryn M. Edwards, Dr. John V. Williams, and Dr. Marie R. Griffin; and the Instituto de Investigacion Nutricional, Lima, Peru: Hector ?Verastegui, Ana I. Gil, and Dr. Claudio F. Lanata.Author ContributionsConceived and designed the experiments: KPK JEV. Performed the experiments: FS SJT JEV. Analyzed the data: FS KPK JEV. Wrote the paper: FS JEV.
Following acute viral or bacterial infection, antigen-specific T cells clonally expand and acquire effector functions that contribute to pathogen clearance. The expansion phase is robust, represent?ing as much as a 50,000?00,000-fold increase from the naive precursor frequency. Following elimination of the pathogen, 90?95 of effector T cells die, leaving behind a long-lived pool of memory T cells. These memory T cells provide protection to subsequent infections with the same or similar pathogens [1]. A major focus of recent study is to determine the molecular signals that control the memory fate decision allowing a minority of effector T cells to survive into the memory pool. CD4+ T cell responses to acute viral or intracellular bacterial infection differ from CD8+ T cell responses with respect to their requirement for TCR-driven differentiation signals. For example, CD8+ T cells require only a short period of antigenic stimulation (6?4 hours) to drive recruitment and programmed differentiation [2?]. CD4+ T cells, on the other hand, require several days of in vivo antigen exposure to achieve maximal expansion and differentiation into pathogen-specific effector cells [6?]. These observations suggest that CD4+ T cells translate TCR signals into a downstream activation/differentiation program in a fundamentally different fashion than do CD8+ T cells. Additionally, the requirement for prolonged exposure to antigen suggests that CD4+ T cell differentiation and survival may be prone to selection on the basis of qualitative and/or quantitative components of the antigen signal [9?1]. One insight into these potential differences between CD4+ and CD8+ T cells came from the observation that CD8+ T cell repertoires are unchanged after the effector phase. For CD8+ T cells, there is no difference in the frequency of distribution ofindividual clonal populations within a pool of cells with a given specificity when comparing effector, memory or secondary effector populations [12]. Conversely, CD4+ T cell repertoires undergo antigen-driven revision and skewing during successive antigen challenges [9,13]. However, one important issue unresolved by these prior studies is how the differentiation and survival of effector cells during the transition into the Th1 memory pool is dependent upon TCR-mediated signals delivered during the primary response, including the amount and duration of antigen, structural avidity of the TCR, the type and maturation state of the antigen presenting cell, and the inflammatory envi.
