B7-1 and B7-2 do not deliver identical costimulatory signals, since B7-2 but not B7-1 preferentially costimulates the initial production of IL-4.
The functional necessity for two CD28 counterreceptors (B7-1 and B7-2) is presently unknown. B7-1 and B7-2 equivalently costimulate IL-2 and interferon-gamma (IFN gamma) production and IL-2 receptor alpha and gamma chain expression. B7-2 induces significantly more IL-4 production than B7-1, with the greatest difference seen in naive T cells. Repetitive costimulation of CD4+ CD45RA+ T cells with B7-2 results in moderate levels of both IL-4 and IL-2, whereas repetitive costimulation with B7-1 results in high levels of IL-2 and low levels of IL-4. Therefore, B7-1 and B7-2 costimulation mediate distinct outcomes, since B7-2 provides an initial signal to induce naive T cells to become IL-4 producers, thereby directing the immune response more towards Th0/Th2, whereas B7-1 is a more neutral differentiative signal.
Freeman
G J
GJ
Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Boussiotis
V A
VA
Anumanthan
A
A
Bernstein
G M
GM
Ke
X Y
XY
Rennert
P D
PD
Gray
G S
GS
Gribben
J G
JG
Nadler
L M
LM
D016475:3T3 Cells; D000818:Animals; D015703:Antigens, CD; D018122:B7-1 Antigen / Q000502:physiology*; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000502:physiology*; D016466:CHO Cells; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D008233:Lymphotoxin-alpha / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D014162:Transfection
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; C497965:Cd86 protein, mouse; D007376:Interleukin-2; D008233:Lymphotoxin-alpha; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens