Stimulation through intercellular adhesion molecule-1 provides a second signal for T cell activation

Area of Science:

• Immunology
• Cellular Signaling
• T cell Activation

Background:

• T cell activation necessitates two signals: antigen presentation via MHC to the T cell receptor (TCR) and a co-stimulatory signal.
• CD28 and LFA-1 are known co-stimulatory receptors on T cells, interacting with B7 and ICAM-1 respectively on other cells.
• The role of ICAM-1 as a co-stimulatory molecule when expressed on the T cell itself, rather than on an interacting cell, was previously uncharacterized.

Purpose of the Study:

• To investigate whether ICAM-1, when present on the T cell surface, can deliver a co-stimulatory signal.
• To characterize the functional consequences of ICAM-1-mediated co-stimulation in T cells.

Main Methods:

• T cells were co-stimulated using anti-CD3 antibodies in combination with anti-ICAM-1 antibodies.
• Assessed T cell proliferation, expression of activation markers (CD69), IL-2 gene transcription, and cytokine secretion.
• Analyzed phosphatidylinositol 3-kinase (PI3K) activation and the proliferative capacity of naive T cells.

Main Results:

• Co-stimulation with anti-CD3 and anti-ICAM-1 significantly increased T cell proliferation, CD69 expression, and IL-2 transcription.
• This co-stimulation led to the secretion of Th1 cytokines and synergistic activation of PI3K.
• Anti-CD3 plus anti-ICAM-1 induced prolonged naive T cell proliferation, mimicking LFA-1 or CD28 co-stimulation.

Conclusions:

• ICAM-1 expressed on the T cell surface can indeed deliver a co-stimulatory signal.
• This ICAM-1-mediated signal enhances T cell activation, proliferation, and cytokine production.
• These findings establish a novel role for T cell-expressed ICAM-1 in regulating T cell responses.