CD28 is required for induction and maintenance of immunological memory in toxin-reactive CD4+ T cells in vivo.
We previously reported that Vbeta3+ CD4+ T cells maintained a protracted expansion, with the phenotypes of memory Th2 cells, for 30 days in C57BL/6 (B6) mice implanted with SEA-containing mini-osmotic pumps. In the present study, we followed the fate of Vbeta3+ CD4+ T cells in CD28-/- mice. Vbeta3+ CD4+ T cells increased to a degree similar to that of B6 Vbeta3+ CD4+ T cells until day 10 after implantation, then declined rapidly reaching the control level by 28 days. Remaining Vbeta3+ CD4+ T cells at that time did not exhibit memory phenotypes nor Th2-deviated responses. The rapid drop in Vbeta3+ CD4+ T cells in CD28-/- mice was attributable to upregulated induction of apoptosis owing to marginal inductions of Bcl-2 and Bcl-xL. Collectively, these data indicate CD28 to play critical roles in the generation and maintenance of SEA-reactive CD4+ T cells in vivo.
Fukada
Kenji
K
Department of Oral and Maxillofacial Surgery, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
Koyanagi
Madoka
M
Arimura
Yutaka
Y
Ogiuchi
Hideki
H
Uchiyama
Takehiko
T
Yagi
Junji
J
D000818:Animals; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D004768:Enterotoxins / Q000494:pharmacology*; D007156:Immunologic Memory / Q000187:drug effects* / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D015854:Up-Regulation
D018106:CD28 Antigens; D004768:Enterotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015847:Interleukin-4; C026066:enterotoxin A, Staphylococcal; D007371:Interferon-gamma