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Distinct costimulatory molecules are required for the induction of effector and memory cytotoxic T lymphocytes.

Liu Y, Wenger RH, Zhao M, Nielsen PJ - J. Exp. Med. (1997)

Bottom Line: Furthermore, our results revealed that B7 is essential for the generation of effector T cells from either naive or memory T cells, while HSA is not necessary for the generation of effector T cells.Our results demonstrate that the induction of memory T cells and effector T cells can utilize distinct costimulatory molecules.These results have important implications on lineage relationship between effector and memory T cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, New York University Medical Center, New York 10016, USA.

ABSTRACT
A successful T cell immune response has two major products: effector T cells which directly or indirectly remove the antigens, and memory T cells, which allow a faster and more efficient recall response when challenged by related antigens. An important issue is whether costimulatory molecules on the antigen-presenting cells are involved in determining whether T cells will differentiate into effector or memory cells after antigenic stimulation. To address this issue, we have produced mice with targeted mutations of either the heat-stable antigen (HSA), or both HSA and CD28. We show that CD28/B7 and HSA provide two alternative costimulatory pathways for induction of immunological memory to influenza virus. Furthermore, our results revealed that B7 is essential for the generation of effector T cells from either naive or memory T cells, while HSA is not necessary for the generation of effector T cells. Our results demonstrate that the induction of memory T cells and effector T cells can utilize distinct costimulatory molecules. These results have important implications on lineage relationship between effector and memory T cells.

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Production of mice homozygous for a disrupted HSA gene.  (a) The disruption of the HSA gene in C57BL/6 ES line BL/6-III was  achieved by replacement of the HSA promotor and the first exon with a  neomycin-resistance expression cassette. The coding portions of both  HSA exons are depicted by filled boxes. (b) Southern blot analysis of HSA  genotypes using a Pvu II fragment located between nucleotides −710,  and −1790 relative to the transcriptional start site of the HSA gene as a  hybridization probe.
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Figure 1: Production of mice homozygous for a disrupted HSA gene. (a) The disruption of the HSA gene in C57BL/6 ES line BL/6-III was achieved by replacement of the HSA promotor and the first exon with a neomycin-resistance expression cassette. The coding portions of both HSA exons are depicted by filled boxes. (b) Southern blot analysis of HSA genotypes using a Pvu II fragment located between nucleotides −710, and −1790 relative to the transcriptional start site of the HSA gene as a hybridization probe.

Mentions: The disruption of the gene for the HSA in C57BL6ES line BL/6-III (50) was achieved by replacing the HSA promotor and the first exon with a neomycin-resistance expression cassette (Fig. 1 a). Except for a somewhat reduced litter size, the mice homozygous for the targeted mutation (HSA-KO) (Fig. 1 b) are indistinguishable from WT control in a conventional mouse facility. We have mated HSA-deficient mice with previously developed CD28deficient mice and generated mice which are deficient in both HSA and CD28. As shown in Fig. 2, normal numbers of CD4 and CD8 T cells are generated in mice deficient for either HSA and/or CD28. Furthermore, the major types of APC, such as B cells, macrophages, and dendritic cells, are produced in normal numbers in all mutant mice. Thus, these mice can be used for studying the role of costimulatory molecules in the generation effector and memory T cells.


Distinct costimulatory molecules are required for the induction of effector and memory cytotoxic T lymphocytes.

Liu Y, Wenger RH, Zhao M, Nielsen PJ - J. Exp. Med. (1997)

Production of mice homozygous for a disrupted HSA gene.  (a) The disruption of the HSA gene in C57BL/6 ES line BL/6-III was  achieved by replacement of the HSA promotor and the first exon with a  neomycin-resistance expression cassette. The coding portions of both  HSA exons are depicted by filled boxes. (b) Southern blot analysis of HSA  genotypes using a Pvu II fragment located between nucleotides −710,  and −1790 relative to the transcriptional start site of the HSA gene as a  hybridization probe.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196124&req=5

Figure 1: Production of mice homozygous for a disrupted HSA gene. (a) The disruption of the HSA gene in C57BL/6 ES line BL/6-III was achieved by replacement of the HSA promotor and the first exon with a neomycin-resistance expression cassette. The coding portions of both HSA exons are depicted by filled boxes. (b) Southern blot analysis of HSA genotypes using a Pvu II fragment located between nucleotides −710, and −1790 relative to the transcriptional start site of the HSA gene as a hybridization probe.
Mentions: The disruption of the gene for the HSA in C57BL6ES line BL/6-III (50) was achieved by replacing the HSA promotor and the first exon with a neomycin-resistance expression cassette (Fig. 1 a). Except for a somewhat reduced litter size, the mice homozygous for the targeted mutation (HSA-KO) (Fig. 1 b) are indistinguishable from WT control in a conventional mouse facility. We have mated HSA-deficient mice with previously developed CD28deficient mice and generated mice which are deficient in both HSA and CD28. As shown in Fig. 2, normal numbers of CD4 and CD8 T cells are generated in mice deficient for either HSA and/or CD28. Furthermore, the major types of APC, such as B cells, macrophages, and dendritic cells, are produced in normal numbers in all mutant mice. Thus, these mice can be used for studying the role of costimulatory molecules in the generation effector and memory T cells.

Bottom Line: Furthermore, our results revealed that B7 is essential for the generation of effector T cells from either naive or memory T cells, while HSA is not necessary for the generation of effector T cells.Our results demonstrate that the induction of memory T cells and effector T cells can utilize distinct costimulatory molecules.These results have important implications on lineage relationship between effector and memory T cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, New York University Medical Center, New York 10016, USA.

ABSTRACT
A successful T cell immune response has two major products: effector T cells which directly or indirectly remove the antigens, and memory T cells, which allow a faster and more efficient recall response when challenged by related antigens. An important issue is whether costimulatory molecules on the antigen-presenting cells are involved in determining whether T cells will differentiate into effector or memory cells after antigenic stimulation. To address this issue, we have produced mice with targeted mutations of either the heat-stable antigen (HSA), or both HSA and CD28. We show that CD28/B7 and HSA provide two alternative costimulatory pathways for induction of immunological memory to influenza virus. Furthermore, our results revealed that B7 is essential for the generation of effector T cells from either naive or memory T cells, while HSA is not necessary for the generation of effector T cells. Our results demonstrate that the induction of memory T cells and effector T cells can utilize distinct costimulatory molecules. These results have important implications on lineage relationship between effector and memory T cells.

Show MeSH
Related in: MedlinePlus