TY - JOUR
T1 - A role for CD28 in lymphopenia-induced proliferation of CD4 T cells
AU - Hagen, Karin A.
AU - Moses, Christina T.
AU - Drasler, Erin F.
AU - Podetz-Pedersen, Kelly M.
AU - Jameson, Stephen C.
AU - Khoruts, Alexander
PY - 2004/9/15
Y1 - 2004/9/15
N2 - The peripheral mechanisms that regulate the size and the repertoire of the T cell compartment during recovery from a lymphopenic state are incompletely understood. In particular, the role of costimulatory signals, such as those provided by CD28, which have a critical importance for the immune response toward foreign Ags in nonlymphopenic animals, has been unclear in lymphopenia-induced proliferation (LIP). In this study, we show that accumulation of highly divided CD4 T cells characterized by great potential to make IFN-γ is significantly delayed in the absence of B7:CD28 costimulation during LIP. Furthermore, CD28-sufficient CD4 T cells show great competitive advantage over CD28-deficient CD4 T cells when transferred together into the same lymphopenic hosts. Administration of CTLA-4-Ig removed this competitive advantage. Interestingly, CTLA-4-Ig treatment resulted in modest inhibition of LIP by CD28-deficient responders, suggesting that some of its effects may be independent of mere B7 blockade.
AB - The peripheral mechanisms that regulate the size and the repertoire of the T cell compartment during recovery from a lymphopenic state are incompletely understood. In particular, the role of costimulatory signals, such as those provided by CD28, which have a critical importance for the immune response toward foreign Ags in nonlymphopenic animals, has been unclear in lymphopenia-induced proliferation (LIP). In this study, we show that accumulation of highly divided CD4 T cells characterized by great potential to make IFN-γ is significantly delayed in the absence of B7:CD28 costimulation during LIP. Furthermore, CD28-sufficient CD4 T cells show great competitive advantage over CD28-deficient CD4 T cells when transferred together into the same lymphopenic hosts. Administration of CTLA-4-Ig removed this competitive advantage. Interestingly, CTLA-4-Ig treatment resulted in modest inhibition of LIP by CD28-deficient responders, suggesting that some of its effects may be independent of mere B7 blockade.
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U2 - 10.4049/jimmunol.173.6.3909
DO - 10.4049/jimmunol.173.6.3909
M3 - Article
C2 - 15356139
AN - SCOPUS:4644317228
SN - 0022-1767
VL - 173
SP - 3909
EP - 3915
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -