Induction of CTL and Nonpolarized Th Cell Responses by CD8α+ and CD8α− Dendritic Cells

Schlecht, Géraldine; Leclerc, Claude; Dadaglio, Gilles

doi:10.4049/jimmunol.167.8.4215

Cited by 28 publications

(18 citation statements)

References 38 publications

(45 reference statements)

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“…Results obtained between neonatal and adult DC are not statistically different using a t test (p ϭ 0.72). adult mice immunized with DC loaded with p 118 -126 which contains both H-2 d class I and class II epitopes (22). The comparable LCMV-specific CTL responses induced by either neonatal or adult DC do suggest that the Th response induced by p 118 -126 -pulsed neonatal DC does not negatively affect the CTL response.…”

Section: Discussionmentioning

confidence: 76%

Efficient In Vivo Priming of Specific Cytotoxic T Cell Responses by Neonatal Dendritic Cells

Dadaglio

Sun

Lo‐Man

et al. 2002

The Journal of Immunology

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In early life, a high susceptibility to infectious diseases as well as a poor capacity to respond to vaccines are generally observed as compared with observations in adults. The mechanisms underlying immune immaturity have not been fully elucidated and could be due to the immaturity of the T/B cell responses and/or to a defect in the nature and quality of Ag presentation by the APC. This prompted us to phenotypically and functionally characterize early life murine dendritic cells (DC) purified from spleens of 7-day-old mice. We showed that neonatal CD11c+ DC express levels of costimulatory molecules and MHC molecules similar to those of adult DC and are able to fully maturate after LPS activation. Furthermore, we demonstrated that neonatal DC can efficiently take up, process, and present Ag to T cells in vitro and induce specific CTL responses in vivo. Although a reduced number of these cells was observed in the spleen of neonatal mice as compared with adults, this study clearly shows that neonatal DC have full functional capacity and may well prime Ag-specific naive T cells in vivo.

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Section: Discussionmentioning

confidence: 76%

Efficient In Vivo Priming of Specific Cytotoxic T Cell Responses by Neonatal Dendritic Cells

Dadaglio

Sun

Lo‐Man

et al. 2002

The Journal of Immunology

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“…However, we and others have found only minor differences in the ability of CD11c high DC subsets to drive Th1/ Th2 development (26,31). In addition, all CD11c high DC subsets can make IL-12 p40 in response to appropriate microbial stimuli, and CD8␣ ϩ and DN DC can also make IL-12 p70, demonstrating that IL-12 production by DC is not restricted to the CD8␣ ϩ subset (32)(33)(34)(35).…”

Section: Endritic Cells (Dc)mentioning

confidence: 99%

“…Functional comparisons of DC subsets have been similarly controversial. Initial observations that CD8␣ ϩ DC are intrinsically tolerogenic (23,24) have been hard to reproduce (25,26). More prevalent has been the idea that CD8␣…”

Section: Endritic Cells (Dc)mentioning

confidence: 99%

Relationships Among Murine CD11chigh Dendritic Cell Subsets as Revealed by Baseline Gene Expression Patterns

Edwards

Chaussabel

Tomlinson

et al. 2003

The Journal of Immunology

120

119

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The functional relationships and properties of different subtypes of dendritic cells (DC) remain largely undefined. To better characterize these cells, we used global gene analysis to determine gene expression patterns among murine CD11chigh DC subsets. CD4+, CD8α+, and CD8α− CD4− (double negative (DN)) DC were purified from spleens of normal C57/BL6 mice and analyzed using Affymetrix microarrays. The CD4+ and CD8α+ DC subsets showed distinct basal expression profiles differing by >200 individual genes. These included known DC subset markers as well as previously unrecognized, differentially expressed CD Ags such as CD1d, CD5, CD22, and CD72. Flow cytometric analysis confirmed differential expression in nine of nine cases, thereby validating the microarray analysis. Interestingly, the microarray expression profiles for DN cells strongly resembled those of CD4+ DC, differing from them by <25 genes. This suggests that CD4+ and DN DC are closely related phylogenetically, whereas CD8α+ DC represent a more distant lineage, supporting the historical distinction between CD8α+ and CD8α− DC. However, staining patterns revealed that in contrast to CD4+ DC, the DN subset is heterogeneous and comprises at least two subpopulations. Gene Ontology and literature mining analyses of genes expressed differentially among DC subsets indicated strong associations with immune response parameters as well as cell differentiation and signaling. Such associations offer clues to possible unique functions of the CD11chigh DC subsets that to date have been difficult to define as rigid distinctions.

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“…Although the types of dendritic cell (CD8␣ ϩ versus CD8␣ Ϫ ) in these two populations are probably different, both populations are equally efficient at inducing antigen-specific CD4 ϩ Th1 responses after i.v. injection in vivo (41). Since no Th1 response was induced by dendritic cells in the CD8 Ϫ population (Fig.…”

Section: Ifn-␥ Produced By Cd8mentioning

confidence: 99%

Novel Role of CD8⁺T Cells and Major Histocompatibility Complex Class I Genes in the Generation of Protective CD4⁺Th1 Responses during Retrovirus Infection in Mice

Peterson

Stromnes

Messer

et al. 2002

J Virol

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CD4؉ Th1 responses to virus infections are often necessary for the development and maintenance of virus-specific CD8 ؉ T-cell responses. However, in the present study with Friend murine retrovirus (FV), the reverse was also found to be true. In the absence of a responder H-2 b allele at major histocompatibility complex (MHC) class II loci, a single H-2D Recovery from virus infections often requires the development of both cell-mediated and humoral immune responses which are regulated by CD4 ϩ helper T cells. CD4 ϩ helper T cells have been divided into two major functional types, Th1 and Th2. Th1 cells have an integral role in protective immunity against virus infections, providing help for the development and maintenance of both cytotoxic T lymphocyte (CTL) and neutralizing antibody responses and also directly suppressing virus replication by the secretion of gamma interferon (IFN-␥) (5,23,43). Th2 responses also provide help for the generation of neutralizing antibody responses but can suppress the development of antiviral Th1 responses through the production of immunosuppressive cytokines like interleukin-10 (IL-10) and/or transforming growth factor ␤ (TGF-␤) (8, 36). Thus, protection against retrovirus infection which requires both cellmediated and humoral effector mechanisms (19) may be favored by the development of a Th1 rather than a Th2 CD4 ϩ T-cell response.Although many factors can direct CD4 ϩ T cells toward a Th1 or Th2 response (9), the regulation of these responses during infection in vivo is not well understood. One factor that has been shown to affect the development of CD4 ϩ Th1 or Th2 responses in vivo is the major histocompatibility complex (MHC) genotype of the host (34). In fact, MHC regulation of these responses can influence whether or not a host recovers from infection with a specific pathogen (2,22). This has been best studied in mice, where the MHC genotypes of inbred strains can determine resistance or susceptibility to infection (28,43). mice is dependent upon the generation of strong immune responses, including FV-specific CD8 ϩ CTLs, neutralizing antibody, and CD4 ϩ T cells (19). The present study examined the effects of different subregions of MHC on FV-specific CD4 ϩ T-cell subsets. As expected, an FV-specific Th1 response was associated with MHC class II genes of the H-2 b haplotype, since MHC class II molecules present peptides which are antigenic to CD4 ϩ T cells (33,35). However, in the absence of H-2 b alleles at the MHC class II loci, a strong FV-specific Th1 response was also associated with an H-2 b allele at the MHC class I locus, H-2D. This surprising effect was mediated by CD8 ϩ T cells, which appeared to exert a helper effect on the CD4 ϩ T-cell response to this virus.

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Induction of CTL and Nonpolarized Th Cell Responses by CD8α+ and CD8α− Dendritic Cells

Cited by 28 publications

References 38 publications

Efficient In Vivo Priming of Specific Cytotoxic T Cell Responses by Neonatal Dendritic Cells

Efficient In Vivo Priming of Specific Cytotoxic T Cell Responses by Neonatal Dendritic Cells

Relationships Among Murine CD11chigh Dendritic Cell Subsets as Revealed by Baseline Gene Expression Patterns

Novel Role of CD8⁺T Cells and Major Histocompatibility Complex Class I Genes in the Generation of Protective CD4⁺Th1 Responses during Retrovirus Infection in Mice

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Induction of CTL and Nonpolarized Th Cell Responses by CD8α+ and CD8α− Dendritic Cells

Cited by 28 publications

References 38 publications

Efficient In Vivo Priming of Specific Cytotoxic T Cell Responses by Neonatal Dendritic Cells

Efficient In Vivo Priming of Specific Cytotoxic T Cell Responses by Neonatal Dendritic Cells

Relationships Among Murine CD11chigh Dendritic Cell Subsets as Revealed by Baseline Gene Expression Patterns

Novel Role of CD8+T Cells and Major Histocompatibility Complex Class I Genes in the Generation of Protective CD4+Th1 Responses during Retrovirus Infection in Mice

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Novel Role of CD8⁺T Cells and Major Histocompatibility Complex Class I Genes in the Generation of Protective CD4⁺Th1 Responses during Retrovirus Infection in Mice