A role for CD28 in lymphopenia-induced proliferation of CD4 T cells.
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-gamma 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.
Hagen
Karin A
KA
Center for Immunology, and Department of Medicine, University of Minnesota, Minneapolis 55455, USA.
Moses
Christina T
CT
Drasler
Erin F
EF
Podetz-Pedersen
Kelly M
KM
Jameson
Stephen C
SC
Khoruts
Alexander
A
D000069594:Abatacept; D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology; D018122:B7-1 Antigen / Q000235:genetics / Q000502:physiology; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000235:genetics / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002469:Cell Separation; D006131:Growth Inhibitors / Q000008:administration & dosage; D018796:Immunoconjugates / Q000008:administration & dosage; D007371:Interferon-gamma / Q000096:biosynthesis; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497965:Cd86 protein, mouse; D006131:Growth Inhibitors; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D015375:Receptors, Interleukin-2; D000069594:Abatacept; D007371:Interferon-gamma