Orally tolerized T cells are only able to enter B cell follicles following challenge with antigen in adjuvant, but they remain unable to provide B cell help

Although it is well documented that feeding Ag can tolerize or prime systemic humoral and cell-mediated immune responses, the mechanisms involved remain unclear. Elucidation of these mechanisms remains, in part, complicated by the inability to assess responses by individual lymphocyte populations. In the past, in vivo studies have examined T cell responses at the gross level by examining their ability to support B cell Ab production. However, as the fed Ag has the capacity to affect B cells directly, analyzing the functional capacity of a single Ag-specific T cell population in vivo has been difficult. Using a double-adoptive transfer system, we have primed or tolerized T cells, independently of B cells with a high dose of fed Ag, and examined the ability of these primed or tolerized T cells to support B cell clonal expansion in response to a conjugated Ag in vivo. We have been able to show that primed T cells support B cell clonal expansion and Ab production whereas tolerized T cells do not. Thus, we have provided direct evidence that tolerized T cells are functionally unable to help B cells in vivo. Furthermore, we have shown that this inability of tolerized T cells to support fulminant B cell responses is not a result of defective clonal expansion or follicular migration, since following challenge tolerized T cells are similar to primed T cells in both of these functions.