CD4+ Th1 and CD8+ type 1 cytotoxic T cells both play a crucial role in the full development of contact hypersensitivity.
The role of CD4(+) vs CD8(+) T cells in contact hypersensitivity (CHS) remains controversial. In this study, we used gene knockout (KO) mice deficient in CD4(+) or CD8(+) T cells to directly address this issue. Mice lacking either CD4(+) or CD8(+) T cells demonstrated depressed CHS responses to dinitrofluorobenzene and oxazolone compared with wild-type C57BL/6 mice. The depression of CHS was more significant in CD8 KO mice than in CD4 KO mice. Furthermore, in vivo depletion of either CD8(+) T cells from CD4 KO mice or CD4(+) T cells from CD8 KO mice virtually abolished CHS responses. Lymph node cells (LNCs) from hapten-sensitized CD4 and CD8 KO mice showed a decreased capacity for transferring CHS. In vitro depletion of either CD4(+) T cells from CD8 KO LNCs or CD8(+) T cells from CD4 KO LNCs resulted in a complete loss of CHS transfer. LNCs from CD4 and CD8 KO mice produced significant amounts of IFN-gamma, indicating that both CD4(+) and CD8(+) T cells are able to secrete IFN-gamma. LNCs from CD8, but not CD4, KO mice were able to produce IL-4 and IL-10, suggesting that IL-4 and IL-10 are mainly derived from CD4(+) T cells. Intracellular cytokine staining of LNCs confirmed that IFN-gamma-positive cells consisted of CD4(+) (Th1) and CD8(+) (type 1 cytotoxic T) T cells, whereas IL-10-positive cells were exclusively CD4(+) (Th2) T cells. Collectively, these results suggest that both CD4(+) Th1 and CD8(+) type 1 cytotoxic T cells are crucial effector cells in CHS responses to dinitrofluorobenzene and oxazolone in C57BL/6 mice.
Wang
B
B
Division of Dermatology, Sunnybrook and Women's College Health Science Centre, Toronto, Ontario, Canada.
Fujisawa
H
H
Zhuang
L
L
Freed
I
I
Howell
B G
BG
Shahid
S
S
Shivji
G M
GM
Mak
T W
TW
Sauder
D N
DN
D000279:Administration, Cutaneous; D019264:Adoptive Transfer; D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis* / Q000235:genetics; D016827:CD8 Antigens / Q000096:biosynthesis* / Q000235:genetics; D003877:Dermatitis, Contact / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D004139:Dinitrofluorobenzene / Q000008:administration & dosage / Q000276:immunology; D007106:Immune Sera / Q000494:pharmacology; D007108:Immune Tolerance / Q000235:genetics; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010081:Oxazolone / Q000008:administration & dosage / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D015704:CD4 Antigens; D016827:CD8 Antigens; D007106:Immune Sera; D016753:Interleukin-10; D010081:Oxazolone; D015847:Interleukin-4; D007371:Interferon-gamma; D004139:Dinitrofluorobenzene