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Critical Reviews™ in Immunology
IF: 1.352 5-Year IF: 3.347 SJR: 0.657 SNIP: 0.55 CiteScore™: 2.19

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v15.i3-4.30
pages 235-253

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

Anette Gjorloff Wingren
The Wallenberg Laboratory, Department of Tumor Immunology, University of Lund, Box 7031, S-220 07, Lund, Sweden
Eduardo Parra
The Wallenberg Laboratory, Department of Tumor Immunology, University of Lund, Box 7031, S-220 07, Lund, Sweden
Mikael Varga
Pharmacia Immunology Oncology, Scheelevägen 22, S-223 63, Lund, Sweden
Terje Kalland
The Wallenberg Laboratory, Department of Tumor Immunology, University of Lund, Box 7031, S-220 07; Pharmacia Immunology Oncology, Scheelevägen 22, S-223 63, Lund, Sweden
Hans-Olov Sjogren
The Wallenberg Laboratory, Department of Tumor Immunology, University of Lund, Box 7031, S-220 07, Lund, Sweden
Gunnar Hedlund
The Wallenberg Laboratory, Department of Tumor Immunology, University of Lund, Box 7031, S-220 07; Pharmacia Immunology Oncology, Scheelevägen 22, S-223 63, Lund, Sweden
Mikael Dohlsten
The Wallenberg Laboratory, Department of Tumor Immunology, University of Lund, Box 7031, S-220 07; Pharmacia Immunology Oncology, Scheelevägen 22, S-223 63, Lund, Sweden

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 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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