SPLEEN-CELLS FROM ANTIGEN-MINIMIZED MICE ARE SUPERIOR TO SPLEEN-CELLSFROM GERM-FREE AND CONVENTIONAL MICE IN THE STIMULATION OF PRIMARY IN-VITRO PROLIFERATIVE RESPONSES TO NOMINAL ANTIGENS

T lymphocytes from mice reared under conditions of differential exposu re to food, environmental and microbial antigens were compared for phe notypic shifts that may be associated with prior exposure to antigens as well as functional variations in the ability to respond to antigens ne novo. While the intra-epithelial CD8 T cell compartment was found to differ significantly in the type of T cell receptor predominantly e xpressed, CD4 T cells from various lymphoid organs of conventionally r eared specific pathogen-free (CL-SPF) mice showed only subtle phenotyp ic differences from cells obtained from antigen-minimized germ-free (A F) and germ-free (GF) mice. Cells derived from mice exposed to a reduc ed antigen load exhibited primary in vitro proliferative responses to antigens such as dinitrophenyl-keyhole limpet hemocyanin which were si gnificantly enhanced when compared with similar responses of cells fro m conventional mice. In cell mixing experiments, differences in the re activity of T cells from the spleens of AF, GF and CL-SPF mice were de pendent on the source of the spleen cells employed as antigen-presenti ng cells (APC). Experiments in which the T cell population was held co nstant revealed that, as APC, spleen cells from AF mice were most ofte n superior to spleen cells from GF mice which were in turn considerabl y better than a similar population from SPF mice. We conclude that the enhanced primary reactivity of spleen cells from AF mice to nominal a ntigen in vitro is likely to be the result of a difference in the func tion and/or regulatory activities of the cell population employed as A PC in this investigation.