RT Journal Article ID 18784355003c164e A1 Wingren, Anette Gjorloff A1 Parra, Eduardo A1 Varga, Mikael A1 Kalland, Terje A1 Sjogren, Hans-Olov A1 Hedlund, Gunnar A1 Dohlsten, Mikael T1 T Cell Activation Pathways: B7, LFA-3, and ICAM-1 Shape Unique T Cell Profiles JF Critical Reviews™ in Immunology JO CRI YR 1995 FD 1995-12-01 VO 15 IS 3-4 SP 235 OP 253 K1 T lymphocytes K1 costimulation K1 B7 K1 LFA-3 K1 ICAM-1 K1 superantigen K1 T helper cell subsets AB 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. PB Begell House LK https://www.dl.begellhouse.com/journals/2ff21abf44b19838,601751ce468f47e1,18784355003c164e.html