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Leukocyte function-associated antigen 1 is an activation molecule for human T cells
M C Wacholtz1, S S Patel, P E Lipsky
1Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75235.
The Journal of Experimental Medicine
|August 1, 1989
Summary
Leukocyte function-associated antigen 1 (LFA-1) engagement alone does not activate T cells. However, LFA-1 costimulation with CD3 amplifies T cell activation, suggesting a role in immune responses.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Leukocyte function-associated antigen 1 (LFA-1) is crucial for cell adhesion and interaction.
- The direct impact of LFA-1 engagement on cellular activation remained largely unexplored.
Purpose of the Study:
- To investigate whether LFA-1 engagement can directly modulate T cell activation.
- To explore the signaling pathways involved in LFA-1 mediated T cell activation.
Main Methods:
- Crosslinking of LFA-1 on human T cell clones using specific antibodies.
- Measurement of intracellular calcium ([Ca2+]i) levels.
- Assays for IL-2 production and [3H]thymidine incorporation to assess T cell activation.
- Studies using T cell clones from patients with leukocyte adhesion deficiency.
Main Results:
- Crosslinking LFA-1 alone did not induce T cell activation (no increase in [Ca2+]i, IL-2 production, or DNA synthesis).
- Co-crosslinking LFA-1 with CD3 resulted in a prolonged calcium signal and significantly augmented IL-2 production and DNA synthesis compared to CD3 crosslinking alone.
- LFA-1 mediated enhancement of T cell activation was observed independently of direct crosslinking to CD3, but required intact bivalent anti-CD3 mAb engagement.
Conclusions:
- LFA-1 engagement can transmit unique signals to T cells, contributing to activation.
- Synergistic signaling occurs when LFA-1 and CD3 are engaged independently.
- LFA-1 interaction with its ligand ICAM-1 likely amplifies T cell activation by providing costimulatory signals during physiologic cell-cell interactions.