Intracellular adhesion molecule-1 modulates β-chemokines and directly costimulates T cells in vivo

Hasegawa

The Journal of Immunology

et al. 2007

The tight-skin (TSK/+) mouse, a genetic model for systemic sclerosis, develops cutaneous fibrosis. Although a fibrillin 1 gene mutation and immunological abnormalities have been demonstrated, the roles of adhesion molecules have not been investigated. To directly assess roles of adhesion molecules in skin fibrosis, TSK/+ mice lacking L-selectin and/or ICAM-1 were generated. The deficiency of ICAM-1, but not L-selectin, significantly suppressed (∼48%) the development of skin sclerosis in TSK/+ mice. Similarly, ICAM-1 antisense oligonucleotides inhibited skin fibrosis in TSK/+ mice. Although T cell infiltration was modest into the skin of TSK/+ mice, ICAM-1 deficiency down-regulated this migration, which is consistent with the established roles of endothelial ICAM-1 in leukocyte infiltration. In addition, altered phenotype or function of skin fibroblasts was remarkable and dependent on ICAM-1 expression in TSK/+ mice. ICAM-1 expression was augmented on TSK/+ dermal fibroblasts stimulated with IL-4. Although growth or collagen synthesis of TSK/+ fibroblasts cultured with IL-4 was up-regulated, it was suppressed by the loss or blocking of ICAM-1. Collagen expression was dependent on the strain of fibroblasts, but not on the strain of cocultured T cells. Thus, our findings indicate that ICAM-1 expression contributes to the development of skin fibrosis in TSK/+ mice, especially via ICAM-1 expressed on skin fibroblasts.

Section: Discussionmentioning

confidence: 99%

Intercellular Adhesion Molecule-1 Deficiency Attenuates the Development of Skin Fibrosis in Tight-Skin Mice

Hasegawa

The Journal of Immunology

et al. 2007

The Journal of Immunology

“…However, the in vivo responses to ICAM-1-mediated costimulation may be more complicated. Kim et al (32) have found that the in vivo expression of ICAM-1, with cDNA expression cassettes, causes enhancement of both immunogen-specific CD4…”

Section: Discussionmentioning

confidence: 99%

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

Gaglia

Greenfield

Mattoo

et al. 2000

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.

Mem. Inst. Oswaldo Cruz

“…An apparent contrary result was also obtained in L. (L.) donovani model of visceral leishmaniasis where CD86 blocking increased IFN-γ production and reduced parasite burden (Murphy et al 1997). A possible explanation for these results is that a more complex picture could be involved in driving lymphocytes to TH1 or TH2 response (Kim et al 1999). Whereas CD80 or CD86 expression leads to high IL-4 and IL-10 production by naive CD4 T cells, co-expression of CD54 plus CD80 or CD 86 resulted in decreased IL-4 and IL-10 production (Luksch et al 1999).…”

Section: Parasite's General Strategy At the Initial Phases Of Leishmamentioning

confidence: 99%

Leishmanial infection: analysis of its first steps. A review

Almeida

Vilhena²,

Barral

et al. 2003