Under normal circumstances most lymphoid cell populations do not exhib
it strong proliferative reactions in culture unless provoked by antige
n or mitogen. The autologous mixed lymphocyte reaction (AMLR) mediated
by adult T cells is a relatively weak proliferative response that occ
urs in the absence of known heterologous stimuli. In this investigatio
n we demonstrate that Peyer's patch (PP) cells possess an inherent cap
acity to commence dividing in vitro and to display an exceptionally vi
gorous AMLR. The magnitude and kinetics of this spontaneous proliferat
ion resemble that of a secondary response to a strong mucosal immunoge
n such as reovirus type 1/Lang. Analysis of the cellular components of
the PP cultures implicates CD4+CD8- T cells as the major responding p
opulation and dendritic cells (DC) as stimulators. Mixing experiments
indicate that spleen contains a cell population which can stimulate PP
T cells, albeit to a lesser extent than PP cells. Similarly, splenic
T cells have a reduced but significant capacity to respond to PP DC, i
n comparison to PP T cells. These differences suggest the possibility
that there may be a decreasing gradient of antigenicity between the gu
t and the spleen which is reflected in the spontaneous activity of PP
versus splenic T cells in vitro. We propose that PP cells are in fact
responding in vitro to heterologous antigens derived from food, enteri
c microbes and other environmental sources. This notion is supported b
y the observation that PP cells from antigen-minimized germ-free mice
fail to proliferate spontaneously in culture.