We have described a unique age-dependent maturational change in the function of the macrophage APC population in SJL mice. All other strains of mice tested have """"""""adult"""""""" levels of delayed type hypersensitivity (DTH) responsiveness by 4 wks of age. SJL are DTH unresponsive until 10 wks of age. No differences were detected in the ability of young adult SJL to respond to Con A, produce IL-2 and antibody or generate allogeneic CTL's when compared to 12 wk SJL. Thus, the defect appears to be specific for DTH responsiveness. Responsiveness can be adoptively transferred from DTH responders to nonresponders with macrophage antigen presenting cells (APC). These data indicate that young adult SJL mice have a unique age-dependent lack of DTH APC function. This proposal will expand these findings to determine if the Th cells in 6 wk SJL are defective using an in vitro DTH system, determine if there is a concomitant defect in B cell-Th cell interactions, or whether the adoptive transfer of APC alters the suppressor network in 6 wk SJL. The data strongly indicates that the defect is in APC function. The role of Ia-antigen expression will be examined both biochemically and functionally. In addition we will determine if the defect is at the level of antigen presentation or processing. These experiments will give insight into the cell-cell interactions involved in the formation of a DTH response, possibly defining the subsets of APC and Th cells involved in the DTH response.
| Sussman, M A; Shubin, R A; Kyuwa, S et al. (1989) T-cell-mediated clearance of mouse hepatitis virus strain JHM from the central nervous system. J Virol 63:3051-6 |
