Intercellular Adhesion Molecule 1 Is Critical for Activation of CD28-Deficient T Cells

Abstract

Presentation of Ag to T lymphocytes in the absence of the requisite costimulatory signals leads to an Ag-specific unresponsiveness termed anergy, whereas Ag presentation in conjunction with costimulation leads to clonal expansion. B7/CD28 signaling has been shown to provide this critical costimulatory signal and blockade of this pathway may inhibit in vitro and in vivo immune responses. Although T cells from CD28-deficient mice are lacking in a variety of responses, they nonetheless are capable of various primary and secondary responses without the induction of anergy expected in the absence of costimulation. This suggests that there may be alternative costimulatory pathways that can replace CD28 signaling under certain circumstances. In this paper, we show that ICAM-1becomes a dominant costimulatory molecule for CD28-deficient T cells. ICAM-1 costimulates anti-CD3-mediated T cell proliferation and IL-2 secretion in CD28-deficient murine T cells. Furthermore, splenocytes from ICAM-1-deficient mice could not activate CD28-deficient T cells and splenocytes lacking both ICAM and CD28 fail to proliferate in response to anti-CD3-induced T cell signals. This confirms that not only can ICAM-1 act as a CD28-independent costimulator, but it is the dominant, requisite costimulatory molecule for the activation of T cells in the absence of B7/CD28 costimulation.

Long-Term Reversal of Established Autoimmunity upon Transient Blockade of the LFA-1/Intercellular Adhesion Molecule-1 Pathway

“…Agonistic effects of sICAM-1 on the ICAM-1/ LFA-1 pathway have already been shown in in vitro systems (29). As expected (29), and in contrast to CD28 binding to B7 costimulatory molecules (30), the increase in IL-2 secretion was slight, confirming a distinct effect on T cell activation through the LFA-1/ICAM-1 pathway as compared with CD28 (31,32). In experiments in which Ad vectors were injected in prediabetic mice, Ad.null injection induced a short, although not statistically significant, delay in overt diabetes.…”

Amplification of the lytic potential of effector/memory CD8+ cells by vector-based enhancement of ICAM-1 (CD54) in target cells: implications for intratumoral vaccine therapy

“…The conjugates were adjusted to 1 Â 10 6 cells/ml and plated on coverslips precoated with poly-L-lysine (Sigma, St Louis, MO). After adherence, the cover slips were washed with PBS and fixed for 1 hour with 4% paraformaldehyde, followed by two quenching steps of 5 minutes each with 50 mM of NH 4 Cl. Cells were permeabilized with 1% NP-40 in wash buffer (PBS þ 3% FCS þ 0.01% saponin) for 10 minutes.…”

“…Although there have been a number of studies on the role of accessory molecules in T-cell activation, [4][5][6][7][8][9][10] only a few studies have begun to address the role of the costimulatory molecules on enhancing the stimulation of effector/memory cells. [11][12][13][14][15] To this end, we have investigated the consequence of infected tumor target cells with fowlpox (FP) viruses containing various costimulatory molecules on enhancing the activity of the effector/memory CD8 þ cells in the lysis of those target cells.…”

Requirement for CD28 May Not Be Absolute for Collagen-Induced Arthritis: Study with HLA-DQ8 Transgenic Mice

“…Additionally, blocking CD28 signaling with CD28 F(ab) ameliorates MBP-induced experimental autoimmune encephalomyelitis (13). However, in the absence of CD28 signaling, other costimulatory molecules can become dominant (14). T cells from CD28 Ϫ/Ϫ mice have greatly reduced in vitro responses, but can be primed to Ag and mount primary and secondary responses.…”