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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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Requirement for costimulatory molecules in the generation of memory T cells assayed at  100 d after priming: microplate culture in the absence of exogenous cytokines. Both WT and HSA-KO  mice were injected with influenza  virus A/JAP (1,000 HAU/mouse)  (day 0) and treated with either a  mixture of hamster and rat Ig or a  mixture of anti-B7-1 plus B7-2 on  days −1, 1, 3, 7, 10, 13, 21 (200 μg/ mAb/injection). At 100 d after the  viral infection, pooled spleen cells  (three mice per group) were stimulated in vitro, CTL activity was determined 5 d after stimulation. Similar  results were obtained when memory  CTL activity was measured at 30 d  after infection.
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Figure 7: Requirement for costimulatory molecules in the generation of memory T cells assayed at 100 d after priming: microplate culture in the absence of exogenous cytokines. Both WT and HSA-KO mice were injected with influenza virus A/JAP (1,000 HAU/mouse) (day 0) and treated with either a mixture of hamster and rat Ig or a mixture of anti-B7-1 plus B7-2 on days −1, 1, 3, 7, 10, 13, 21 (200 μg/ mAb/injection). At 100 d after the viral infection, pooled spleen cells (three mice per group) were stimulated in vitro, CTL activity was determined 5 d after stimulation. Similar results were obtained when memory CTL activity was measured at 30 d after infection.

Mentions: T cells responsible for long-term memory may be different from those for the early recall response measured here (54, 55). Since the above experiments used spleen cells that were primed only 8 d previously, we treated both WT and HSA-KO mice with anti-B7 mAbs for 3 wk and waited 100 d after immunization before harvesting spleen cells and assaying for memory cells in an in vitro recall culture. As shown in Fig. 7, while repeated treatment with anti-B7 mAbs reduced the recall CTL activity in the WT mice, there still were very potent recall CTL responses in such anti-B7-treated mice. In fact, the numbers of responder cells required for detectable recall responses in vitro were similar in both groups. In contrast, in HSA-KO mice, injection of a mixture of anti-B7 mAbs eliminated the generation of memory cells. These results demonstrate that costimulation by either B7 or HSA alone is sufficient for induction of memory T cells, regardless of when the memory activity is determined. The lack of longterm memory in anti-B7 treated HSA-KO mice rules out the possibility that memory cells are produced after decay of the antibodies in vivo. Moreover, the production of memory cells in anti-B7-treated WT mice depends on HSA. Thus, the induction of T cells responsible for rapid priming of recall CTL responses and long-term memory responses has a similar requirement for costimulatory molecules; either B7 or HSA can provide costimulation for induction of 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)

Requirement for costimulatory molecules in the generation of memory T cells assayed at  100 d after priming: microplate culture in the absence of exogenous cytokines. Both WT and HSA-KO  mice were injected with influenza  virus A/JAP (1,000 HAU/mouse)  (day 0) and treated with either a  mixture of hamster and rat Ig or a  mixture of anti-B7-1 plus B7-2 on  days −1, 1, 3, 7, 10, 13, 21 (200 μg/ mAb/injection). At 100 d after the  viral infection, pooled spleen cells  (three mice per group) were stimulated in vitro, CTL activity was determined 5 d after stimulation. Similar  results were obtained when memory  CTL activity was measured at 30 d  after infection.
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Related In: Results  -  Collection

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Figure 7: Requirement for costimulatory molecules in the generation of memory T cells assayed at 100 d after priming: microplate culture in the absence of exogenous cytokines. Both WT and HSA-KO mice were injected with influenza virus A/JAP (1,000 HAU/mouse) (day 0) and treated with either a mixture of hamster and rat Ig or a mixture of anti-B7-1 plus B7-2 on days −1, 1, 3, 7, 10, 13, 21 (200 μg/ mAb/injection). At 100 d after the viral infection, pooled spleen cells (three mice per group) were stimulated in vitro, CTL activity was determined 5 d after stimulation. Similar results were obtained when memory CTL activity was measured at 30 d after infection.
Mentions: T cells responsible for long-term memory may be different from those for the early recall response measured here (54, 55). Since the above experiments used spleen cells that were primed only 8 d previously, we treated both WT and HSA-KO mice with anti-B7 mAbs for 3 wk and waited 100 d after immunization before harvesting spleen cells and assaying for memory cells in an in vitro recall culture. As shown in Fig. 7, while repeated treatment with anti-B7 mAbs reduced the recall CTL activity in the WT mice, there still were very potent recall CTL responses in such anti-B7-treated mice. In fact, the numbers of responder cells required for detectable recall responses in vitro were similar in both groups. In contrast, in HSA-KO mice, injection of a mixture of anti-B7 mAbs eliminated the generation of memory cells. These results demonstrate that costimulation by either B7 or HSA alone is sufficient for induction of memory T cells, regardless of when the memory activity is determined. The lack of longterm memory in anti-B7 treated HSA-KO mice rules out the possibility that memory cells are produced after decay of the antibodies in vivo. Moreover, the production of memory cells in anti-B7-treated WT mice depends on HSA. Thus, the induction of T cells responsible for rapid priming of recall CTL responses and long-term memory responses has a similar requirement for costimulatory molecules; either B7 or HSA can provide costimulation for induction of 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