Active Participation of Antigen-Nonspecific Lymphoid Cells in Immune-Mediated Inflammation

Abstract

The pathogenic process of tissue-specific autoimmune disease depends to a large extent on recruitment of Ag-nonspecific cells into the target tissue. Little is known, however, about the recruitment process and the features that characterize the recruited cells. In this study, we analyzed the recruitment of Ag-nonspecific lymphoid cells into an inflammatory site by using an experimental system in which TCR-transgenic Th1 cells are adoptively transferred to induce ocular inflammation in recipient mice that express the target Ag in their eyes. A sharp increase in number of all host cell populations was observed in the recipient spleen, reaching a peak on day 4 postcell transfer and declining thereafter. A large portion of the host’s spleen CD4 cells underwent phenotypic changes that facilitate their migration into the target organ, the eye. These changes included increased expression of the chemokine receptor CXCR3, and the adhesion molecule CD49d, as well as a decline in expression of CD62L. The host lymphocytes migrated into the recipient mouse eye more slowly than the donor cells, but became the great majority of the infiltrating cells at the peak of inflammation on day 7 postcell injection. Interestingly, the mass migration of host T cells was preceded by an influx of host dendritic cells, that reached their peak on day 4 postcell injection. The eye-infiltrating host CD4 lymphocytes underwent additional changes, acquiring a profile of activated lymphocytes, i.e., up-regulation of CD25 and CD69. Our results thus provide new information about the active participation of Ag-nonspecific lymphoid cells in immune-mediated inflammation.

Phenotypes of Th lineages generated by the commonly used activation with anti-CD3/CD28 antibodies differ from those generated by the physiological activation with the specific antigen

“…We have previously shown that major portions of adoptively transferred activated and pathogenic Th cells specific to HEL migrate to the recipient’s spleen, where they proliferate 17 , prior to their invasion of the eye, the only organ in which the target Ag, HEL, is expressed in this line of Tg mice 18 . The Th transferred cells in our experimental system are traced in the recipient mouse by a clonotypic monoclonal Ab, “1G12”, specific to the Tg TCR of these cells.…”

Type I Interferon Therapy Limits CNS Autoimmunity by Inhibiting CXCR3-Mediated Trafficking of Pathogenic Effector T Cells

“…Parallel T cell subsets have also been described in uveitis patients and in mouse models of CNS autoimmune diseases (Murphy and Stockinger, 2010; Okada, 2006; Shi et al, 2008; Takase et al, 2006). We have established a T cell-transfer model of experimental uveitis in which inflammation is induced by the adoptive transfer of in vitro -primed T cell receptor transgenic (TCR Tg) 3A9 effector T cells that express a TCR against hen egg lysozyme (HEL) into neo-antigen Tg mice that express HEL in their eyes (Chen et al, 2004, 2006). Using this model, we previously reported that disease pathogenesis is dependent on autopathogenic effector CD4 + T cells co-expressing CXCR3 and IFN-γ (Chen et al, 2004, 2006).…”

“…We have established a T cell-transfer model of experimental uveitis in which inflammation is induced by the adoptive transfer of in vitro -primed T cell receptor transgenic (TCR Tg) 3A9 effector T cells that express a TCR against hen egg lysozyme (HEL) into neo-antigen Tg mice that express HEL in their eyes (Chen et al, 2004, 2006). Using this model, we previously reported that disease pathogenesis is dependent on autopathogenic effector CD4 + T cells co-expressing CXCR3 and IFN-γ (Chen et al, 2004, 2006). Given that type I IFNs in treating human MS and experimental autoimmune encephalomyelitis (EAE) have been found effective, we set out to examine the modulatory effects of type I IFNs on the disease pathogenesis of autoimmune uveitis and to define the underlying mechanisms.…”

A Potential Shift From Adaptive Immune Activity to Nonspecific Inflammatory Activation Associated With Higher Depression Symptoms in Chronic Heart Failure Patients

“…Chemokines are essential for providing signaling to leukocytes for extravasation from the blood and directed locomotion. 24,25 When overexpressed, recruitment and migration factors are injurious to the cardiovascular system 26 and can generate angiogenesis and fibrous tissue deposition, which can lead to myocardial dysfunction in CHF. 27,28…”