Differential capacities of CD4+, CD8+, and CD4-CD8- T cell subsets to express IL-18 receptor and produce IFN-gamma in response to IL-18.
IL-12 and IL-18 have the capacity to stimulate IFN-gamma production by T cells. Using a T cell clone, we reported that IL-18 responsiveness is generated only after exposure to IL-12. Here, we investigated the induction of IL-18 responsiveness in resting CD8+, CD4+, and CD4-CD8- T cells. Resting T cells respond to neither IL-12 nor IL-18. After stimulation with anti-CD3 plus anti-CD28 mAbs, CD8+, CD4+, and CD4-CD8- T cells expressed IL-12R, but not IL-18R, and produced IFN-gamma in response to IL-12. Cultures of T cells with anti-CD3/anti-CD28 in the presence of rIL-12 induced IL-18R expression and IL-18-stimulated IFN-gamma production, which reached higher levels than that induced by IL-12 stimulation. However, there was a substantial difference in the expression of IL-18R and IL-18-stimulated IFN-gamma production among T cell subsets. CD4+ cells expressed marginal levels of IL-18R and produced small amounts of IFN-gamma, whereas CD8+ cells expressed higher levels of IL-18R and produced more IFN-gamma than CD4+ cells. Moreover, CD4-CD8- cells expressed levels of IL-18R comparable to those for CD8+ cells but produced IFN-gamma one order higher than did CD8+ cells. These results indicate that the induction of IL-18R and IL-18 responsiveness by IL-12 represents a mechanism underlying enhanced IFN-gamma production by resting T cells, but the operation of this mechanism differs depending on the T cell subset stimulated.
Tomura
M
M
Biomedical Research Center, Osaka University Medical School, Suita, Japan.
Maruo
S
S
Mu
J
J
Zhou
X Y
XY
Ahn
H J
HJ
Hamaoka
T
T
Okamura
H
H
Nakanishi
K
K
Clark
S
S
Kurimoto
M
M
Fujiwara
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000494:pharmacology; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018123:Receptors, Interleukin / Q000378:metabolism*; D053724:Receptors, Interleukin-18; D011994:Recombinant Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; C508573:Il18r1 protein, mouse; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma