TCR-independent activation of extrathymically developed, self antigen-specific T cells by IL-2/IL-15.
Naive intrathymically developed T cells, which express foreign Ag-specific TCR, do not express IL-2R. After antigenic stimulation, they express high affinity IL-2R, which enables IL-2 to be used as an autocrine growth factor. On the contrary, extrathymically developed T cells, which express self Ag-specific TCR but are unresponsive to antigenic stimulation, spontaneously express low affinity IL-2R. In this study, we compared the responses of these two subsets of T cells to IL-2R stimulation and examined the influences of TCR-mediated signaling on the responses. IL-2 or IL-15 augmented the proliferative response of Ag-stimulated, intrathymically developed T cells. On the other hand, extrathymically developed T cells proliferated in response to IL-2 or IL-15, independently of Ag stimulation. Furthermore, both IL-2 and IL-15 induced IFN-gamma production of these T cells, which is strikingly augmented by the presence of IL-12. These results revealed functional differences between intrathymically developed, foreign Ag-specific T cells and extrathymically developed, self Ag-specific T cells. The latter can be activated by some inflammatory cytokines, in an Ag-independent manner, similar to NK cells.
Yamada
H
H
Department of Orthopedic Surgery, Graduate School of Medical Sciences, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan. hisako@bioreg.kyushu-u.ac.jp
Nakamura
T
T
Matsuzaki
G
G
Iwamoto
Y
Y
Nomoto
K
K
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D006182:H-Y Antigen / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D019409:Interleukin-15 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006182:H-Y Antigen; D019409:Interleukin-15; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell