CD28 dependence of T cell differentiation to IL-4 production varies with the particular type 2 immune response.
T cell differentiation to effector cell function is required for the development of a type 2 immune response. The T cell surface molecule, CD28, is widely considered to be the principal costimulatory molecule involved in T cell differentiation to effector function, including IL-4 production, although this has been difficult to directly examine in vivo. We have studied in vivo differentiation to T cell effector function during two type 2 immune responses in CD28 knockout mice: the systemic immune response to goat anti-mouse IgD Ab and the mucosal immune response following oral inoculation with the nematode parasite, Heligmosomoides polygyrus. Our results show that in C57BL/6 CD28 knockout mice elevations in IL-4 gene expression and protein secretion are blocked during the immune response to goat anti-mouse IgD, and associated increases in serum IgG1 and IgE are also inhibited to untreated control levels. In marked contrast, T cell differentiation to IL-4 production is comparable in C57BL/6 CD28 -/- and CD28 +/+ H. polygyrus-inoculated mice, and elevations in both serum IgG1 and IgE levels occur. These results indicate that the specific kind of type 2 immune response determines whether T cell differentiation to IL-4 production is CD28 dependent.
Gause
W C
WC
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. Gause@USUHSB.USUHS.mil
Chen
S J
SJ
Greenwald
R J
RJ
Halvorson
M J
MJ
Lu
P
P
Zhou
X D
XD
Morris
S C
SC
Lee
K P
KP
June
C H
CH
Finkelman
F D
FD
Urban
J F
JF
Abe
R
R
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D018106:CD28 Antigens / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D016207:Cytokines / Q000235:genetics; D005260:Female; D018928:Immunity, Mucosal; D007072:Immunoglobulin D / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis*; D008198:Lymph Nodes / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009351:Nematospiroides dubius / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000947:Antigens, Helminth; D018106:CD28 Antigens; D016207:Cytokines; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D012333:RNA, Messenger; D015847:Interleukin-4; D007073:Immunoglobulin E