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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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B7, but not HSA, plays an important role in the induction of effector T cells from memory T cells, regardless of the priming conditions: microplate culture in the absence of exogenous cytokines. Spleen cells from either WT (a and b) or HSA-deficient mice (c and d) pretreated with either normal Ig  (a and c) or a mixture of anti-B7-1 and anti-B7-2 (b and d) were infected with A/JAP virus as detailed in the legend to Fig. 3. Increasing numbers of  spleen cells were stimulated in vitro for 5 d with A/JAP-infected spleen cells, in the presence of either medium, or a mixture of anti-B7-1 and anti-B7-2, or  anti-HSA mAb (final concentration at 5 μg/ml), and CTL activity was determined in a 6-h 51Cr-release assay. Representative of three independent experiments are shown. Similar results were obtained when memory activity is measured in bulk cultures.
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Figure 8: B7, but not HSA, plays an important role in the induction of effector T cells from memory T cells, regardless of the priming conditions: microplate culture in the absence of exogenous cytokines. Spleen cells from either WT (a and b) or HSA-deficient mice (c and d) pretreated with either normal Ig (a and c) or a mixture of anti-B7-1 and anti-B7-2 (b and d) were infected with A/JAP virus as detailed in the legend to Fig. 3. Increasing numbers of spleen cells were stimulated in vitro for 5 d with A/JAP-infected spleen cells, in the presence of either medium, or a mixture of anti-B7-1 and anti-B7-2, or anti-HSA mAb (final concentration at 5 μg/ml), and CTL activity was determined in a 6-h 51Cr-release assay. Representative of three independent experiments are shown. Similar results were obtained when memory activity is measured in bulk cultures.

Mentions: The activation of memory T cells gives rise to effector T cells. To test whether this process requires costimulatory molecules, we stimulated primed spleen cells in the presence of mAb against either B7 or HSA. As shown in Fig. 8 a, for spleen cells primed when both B7 and HSA-costimulation pathways are intact, the recall response requires costimulation by B7, but not the HSA. To test whether priming conditions affect the requirement for costimulatory molecules in eliciting effector CTL from memory T cells, spleen cells primed when B7 or HSA was blocked were restimulated in the presence of anti-HSA or anti-B7 mAbs. Again, T cells primed in the absence of costimulation by either B7 or HSA require costimulation by B7 for a recall response (Fig. 8, b and c). No recall CTL can be detected in microculture when both B7 and HSA are blocked during priming (Figs. 4 and 8 d). Thus, regardless of the priming conditions, B7 but not HSA is essential for eliciting effector from 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)

B7, but not HSA, plays an important role in the induction of effector T cells from memory T cells, regardless of the priming conditions: microplate culture in the absence of exogenous cytokines. Spleen cells from either WT (a and b) or HSA-deficient mice (c and d) pretreated with either normal Ig  (a and c) or a mixture of anti-B7-1 and anti-B7-2 (b and d) were infected with A/JAP virus as detailed in the legend to Fig. 3. Increasing numbers of  spleen cells were stimulated in vitro for 5 d with A/JAP-infected spleen cells, in the presence of either medium, or a mixture of anti-B7-1 and anti-B7-2, or  anti-HSA mAb (final concentration at 5 μg/ml), and CTL activity was determined in a 6-h 51Cr-release assay. Representative of three independent experiments are shown. Similar results were obtained when memory activity is measured in bulk cultures.
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Related In: Results  -  Collection

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Figure 8: B7, but not HSA, plays an important role in the induction of effector T cells from memory T cells, regardless of the priming conditions: microplate culture in the absence of exogenous cytokines. Spleen cells from either WT (a and b) or HSA-deficient mice (c and d) pretreated with either normal Ig (a and c) or a mixture of anti-B7-1 and anti-B7-2 (b and d) were infected with A/JAP virus as detailed in the legend to Fig. 3. Increasing numbers of spleen cells were stimulated in vitro for 5 d with A/JAP-infected spleen cells, in the presence of either medium, or a mixture of anti-B7-1 and anti-B7-2, or anti-HSA mAb (final concentration at 5 μg/ml), and CTL activity was determined in a 6-h 51Cr-release assay. Representative of three independent experiments are shown. Similar results were obtained when memory activity is measured in bulk cultures.
Mentions: The activation of memory T cells gives rise to effector T cells. To test whether this process requires costimulatory molecules, we stimulated primed spleen cells in the presence of mAb against either B7 or HSA. As shown in Fig. 8 a, for spleen cells primed when both B7 and HSA-costimulation pathways are intact, the recall response requires costimulation by B7, but not the HSA. To test whether priming conditions affect the requirement for costimulatory molecules in eliciting effector CTL from memory T cells, spleen cells primed when B7 or HSA was blocked were restimulated in the presence of anti-HSA or anti-B7 mAbs. Again, T cells primed in the absence of costimulation by either B7 or HSA require costimulation by B7 for a recall response (Fig. 8, b and c). No recall CTL can be detected in microculture when both B7 and HSA are blocked during priming (Figs. 4 and 8 d). Thus, regardless of the priming conditions, B7 but not HSA is essential for eliciting effector from 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