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T Cell Activation Pathways : B7, LFA-3, and ICAM-1 Shape Unique T Cell Profiles

Wingren, Anette Gjorloff LU ; Parra, Eduardo; Varga, Mikael; Kalland, Terje; Sjogren, Hans Olov LU ; Hedlund, Gunnar and Dohlsten, Mikael (2017) In Critical Reviews in Immunology 37(2-6). p.463-481
Abstract

Two signals are required for induction of cell proliferation and cytokine production in resting T cells. Occupancy of the T cell receptor by antigen/MHC complexes delivers the first signal to the T cell, while the second signal is provided by interaction with costimulatory ligands on APC. CD2, LFA-1, and CD28 are the major costimulatory and adhesive molecules on T cells and bind to the LFA-3, ICAM-1 and B7 ligands, respectively, on APC. LFA-3 plays a central role for naive and memory T helper cells during the early phase of an immune response. The LFA-3/CD2 pathway initiates strong antigen-independent cell adhesion, substantial expansion of naive T helper cells, and induction of large amounts of IFN-γ in memory cells. The release of... (More)

Two signals are required for induction of cell proliferation and cytokine production in resting T cells. Occupancy of the T cell receptor by antigen/MHC complexes delivers the first signal to the T cell, while the second signal is provided by interaction with costimulatory ligands on APC. CD2, LFA-1, and CD28 are the major costimulatory and adhesive molecules on T cells and bind to the LFA-3, ICAM-1 and B7 ligands, respectively, on APC. LFA-3 plays a central role for naive and memory T helper cells during the early phase of an immune response. The LFA-3/CD2 pathway initiates strong antigen-independent cell adhesion, substantial expansion of naive T helper cells, and induction of large amounts of IFN-γ in memory cells. The release of IFN-γ may upregulate expression of ICAM-1 and B7 on APC and allows multiple adhesion pathways to amplify the immune response. The LFA- 1/ICAM-l pathway stimulates adhesion and cell proliferation more efficiently in memory T helper cells than in naive cells. Further, the results suggest that naive T helper cells express functionally inactive LFA-1 molecules on the cell surface, which may have a physiological role in keeping these cells in a resting state. B7 costimulation superinduces IL-2 production in both naive and memory T helper cells and generates long-lasting cell proliferation. This permits transition from an autocrine to a paracrine immune response. Coexpression of B7/LFA-3 provides an optimal APC function and enables a vigorous T cell response to minute amounts of antigen. AP-1 and NF-κB transcription factors are involved in the induction of several cytokine gene promoters and play a central role in the regulation of IL-2 gene transcription. LFA-3 costimulation only moderately enhances AP-1 DNA-binding activity and does not influence the NF-κB activity induced by TCR engagement, whereas B7 costimulation induces large amounts of NF-κB and AP-1 activity in T helper cells. The costimulatory ligands represent a family of adhesion molecules with considerable redundancy. Interfamily redundancy of LFA-3, B7, and ICAM ligands offers an opportunity to regulate distinct T cell response profiles in various microenvironments at separate time points of an immune response.

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author
organization
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type
Contribution to journal
publication status
published
subject
in
Critical Reviews in Immunology
volume
37
issue
2-6
pages
19 pages
publisher
Begell House
external identifiers
  • scopus:85059234052
ISSN
1040-8401
DOI
10.1615/CritRevImmunol.v37.i2-6.130
language
English
LU publication?
yes
id
38558c2f-5bfd-47ab-a03c-3fe37a3d69a9
date added to LUP
2019-01-18 11:02:02
date last changed
2019-02-20 11:43:32
@article{38558c2f-5bfd-47ab-a03c-3fe37a3d69a9,
  abstract     = {<p>Two signals are required for induction of cell proliferation and cytokine production in resting T cells. Occupancy of the T cell receptor by antigen/MHC complexes delivers the first signal to the T cell, while the second signal is provided by interaction with costimulatory ligands on APC. CD2, LFA-1, and CD28 are the major costimulatory and adhesive molecules on T cells and bind to the LFA-3, ICAM-1 and B7 ligands, respectively, on APC. LFA-3 plays a central role for naive and memory T helper cells during the early phase of an immune response. The LFA-3/CD2 pathway initiates strong antigen-independent cell adhesion, substantial expansion of naive T helper cells, and induction of large amounts of IFN-γ in memory cells. The release of IFN-γ may upregulate expression of ICAM-1 and B7 on APC and allows multiple adhesion pathways to amplify the immune response. The LFA- 1/ICAM-l pathway stimulates adhesion and cell proliferation more efficiently in memory T helper cells than in naive cells. Further, the results suggest that naive T helper cells express functionally inactive LFA-1 molecules on the cell surface, which may have a physiological role in keeping these cells in a resting state. B7 costimulation superinduces IL-2 production in both naive and memory T helper cells and generates long-lasting cell proliferation. This permits transition from an autocrine to a paracrine immune response. Coexpression of B7/LFA-3 provides an optimal APC function and enables a vigorous T cell response to minute amounts of antigen. AP-1 and NF-κB transcription factors are involved in the induction of several cytokine gene promoters and play a central role in the regulation of IL-2 gene transcription. LFA-3 costimulation only moderately enhances AP-1 DNA-binding activity and does not influence the NF-κB activity induced by TCR engagement, whereas B7 costimulation induces large amounts of NF-κB and AP-1 activity in T helper cells. The costimulatory ligands represent a family of adhesion molecules with considerable redundancy. Interfamily redundancy of LFA-3, B7, and ICAM ligands offers an opportunity to regulate distinct T cell response profiles in various microenvironments at separate time points of an immune response.</p>},
  author       = {Wingren, Anette Gjorloff and Parra, Eduardo and Varga, Mikael and Kalland, Terje and Sjogren, Hans Olov and Hedlund, Gunnar and Dohlsten, Mikael},
  issn         = {1040-8401},
  language     = {eng},
  number       = {2-6},
  pages        = {463--481},
  publisher    = {Begell House},
  series       = {Critical Reviews in Immunology},
  title        = {T Cell Activation Pathways : B7, LFA-3, and ICAM-1 Shape Unique T Cell Profiles},
  url          = {http://dx.doi.org/10.1615/CritRevImmunol.v37.i2-6.130},
  volume       = {37},
  year         = {2017},
}