Srm. Clarke et Ay. Rudensky, Survival and homeostatic proliferation of naive peripheral CD4(+) T cells in the absence of self peptide : MHC complexes, J IMMUNOL, 165(5), 2000, pp. 2458-2464
TCR-self peptide:MHC interactions play a critical role in thymic positive s
election, yet relatively little is known of their function in the periphery
. It has been suggested that continued contact with selecting MHC molecules
is necessary for long-term peripheral maintenance of naive T cells. More r
ecent studies have also demonstrated a role for specific self peptide:MHC c
omplexes in the homeostatic expansion of naive T cells in lymphopenic mice.
Our examination of these processes revealed that, whereas self class II MH
C molecules do have a modest effect on long-term survival of individual CD4
(+) T cells, interactions with specific TCR ligands are not required for pe
ripheral naive CD4(+) T cell maintenance. In contrast, selective engagement
of TCRs by self-peptide:MHC complexes does promote proliferation of CD4(+)
T cells under severe lymphopenic conditions, and this division Is associat
ed with an activation marker phenotype that is different from that induced
by antigenic stimulation. Importantly, however, the ability of naive T tell
s to divide in response to homeostatic stimuli does not appear to be string
ently dependent on TCR-self peptide:MHC interactions. Therefore, these resu
lts show that the factors regulating survival and homeostatic expansion of
naive T cells in the periphery are not identical. In addition, we provide e
vidence for a novel form of T cell proliferation that can occur independent
ly of TCR signaling and suggest that this reflects another mechanism regula
ting homeostatic T cell expansion.