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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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A model for the involvement of costimulatory signals in the  generation of effector and memory T cells. Two major products, effector  and memory T cells, are produced from naive T cells after viral infection.  The production of memory T cells requires costimulation by either HSA  or B7, while the production of effector T cells utilizes B7 but not HSA.  By definition, memory T cells give rise to effector T cells after further  stimulation by antigen. However, effector T cells are unlikely to be mandatory precursors for memory T cells and distinct costimulatory molecules  could be used at different phases of the immune response.
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Figure 9: A model for the involvement of costimulatory signals in the generation of effector and memory T cells. Two major products, effector and memory T cells, are produced from naive T cells after viral infection. The production of memory T cells requires costimulation by either HSA or B7, while the production of effector T cells utilizes B7 but not HSA. By definition, memory T cells give rise to effector T cells after further stimulation by antigen. However, effector T cells are unlikely to be mandatory precursors for memory T cells and distinct costimulatory molecules could be used at different phases of the immune response.

Mentions: A successful adaptive immune response has two major T cell products: effector T cells and memory T cells. The lineage relationship between these two types of cells has not been resolved. Because effector T cells and memory T cells share certain activation conditions (64) and express several identical activation markers (65), it has been proposed that memory T cells are derived from effector T cells (55, 64, 65). A critical prediction of this hypothesis is that memory T cell responses should be eliminated when the effector T cell responses are abrogated. Results presented in this study show that memory CTL responses are largely intact when effector T cell development is completely absent. These results are not consistent with the notion that effector T cells are mandatory precursors for memory T cells. Furthermore, we showed that costimulation by HSA does not contribute to generation of effector cells, but it can and does contribute to the generation of memory cells. This qualitative difference in costimulatory molecules used for effector vs memory T cell responses strongly suggests that these two types of cells can be products of different activation pathways (see Fig. 9 for a model).


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)

A model for the involvement of costimulatory signals in the  generation of effector and memory T cells. Two major products, effector  and memory T cells, are produced from naive T cells after viral infection.  The production of memory T cells requires costimulation by either HSA  or B7, while the production of effector T cells utilizes B7 but not HSA.  By definition, memory T cells give rise to effector T cells after further  stimulation by antigen. However, effector T cells are unlikely to be mandatory precursors for memory T cells and distinct costimulatory molecules  could be used at different phases of the immune response.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 9: A model for the involvement of costimulatory signals in the generation of effector and memory T cells. Two major products, effector and memory T cells, are produced from naive T cells after viral infection. The production of memory T cells requires costimulation by either HSA or B7, while the production of effector T cells utilizes B7 but not HSA. By definition, memory T cells give rise to effector T cells after further stimulation by antigen. However, effector T cells are unlikely to be mandatory precursors for memory T cells and distinct costimulatory molecules could be used at different phases of the immune response.
Mentions: A successful adaptive immune response has two major T cell products: effector T cells and memory T cells. The lineage relationship between these two types of cells has not been resolved. Because effector T cells and memory T cells share certain activation conditions (64) and express several identical activation markers (65), it has been proposed that memory T cells are derived from effector T cells (55, 64, 65). A critical prediction of this hypothesis is that memory T cell responses should be eliminated when the effector T cell responses are abrogated. Results presented in this study show that memory CTL responses are largely intact when effector T cell development is completely absent. These results are not consistent with the notion that effector T cells are mandatory precursors for memory T cells. Furthermore, we showed that costimulation by HSA does not contribute to generation of effector cells, but it can and does contribute to the generation of memory cells. This qualitative difference in costimulatory molecules used for effector vs memory T cell responses strongly suggests that these two types of cells can be products of different activation pathways (see Fig. 9 for a model).

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