Active participation of antigen-nonspecific lymphoid cells in immune-mediated inflammation

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.