A T cell activation antigen, Ly6C, induced on CD4+ Th1 cells mediates an inhibitory signal for secretion of IL-2 and proliferation in peripheral immune responses.
A T cell activation antigen, Ly6C, is considered to be involved in the autoimmunity of some autoimmune-prone mice; however, the function of Ly6C remains largely unknown. We prepared a rat anti-mouse Ly6C monoclonal antibody (mAb) (S14) that inhibits the proliferation of peripheral T cells stimulated with anti-CD3 mAb in vitro. S14 mAb, the specificity of which is confirmed by a cDNA transfectant, recognizes Ly6C antigen preferentially expressed on a part of CD8+ T cells in peripheral lymphoid organs. The immunohistochemical analysis demonstrates that Ly6C appears on CD8+ T cells in the conventional T cell-associated area of BALB/c but not of nonobese diabetic (NOD) mice, confirming the absence of Ly6C+ T cells in NOD mice. Addition of soluble S14 mAb to the culture does not influence the proliferation of T cells in vitro; however, the S14 mAb coated on the plate clearly inhibits the proliferation and IL-2 production of anti-CD3-stimulated peripheral T cells. The T cells are arrested at the transitional stage from G0/G1 to S+G2/M phases, but they are not induced to undergo apoptotic changes in vitro. This inhibitory signal provided through the Ly6C molecule inhibited IL-2 secretion in a subpopulation of the activated CD4+ T cells. Ly6C is expressed on T cell clones of both Th1 and Th2 cells, but the cytokine secretion from Th1 clones is preferentially inhibited. These results suggest that Ly6C mediates an inhibitory signal for secretion of cytokines from Th1 CD4+ T cells, potentially causing the inhibition of immune response in peripheral lymphoid tissues.
Yamanouchi
S
S
Department of Immunology, Kumamoto University School of Medicine, Honjo, Japan.
Kuwahara
K
K
Sakata
A
A
Ezaki
T
T
Matsuoka
S
S
Miyazaki
J
J
Hirose
S
S
Tamura
T
T
Nariuchi
H
H
Sakaguchi
N
N
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology; D000950:Antigens, Ly / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism*; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D051381:Rats; D011917:Rats, Inbred Lew; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D017252:CD3 Complex; D015704:CD4 Antigens; D007376:Interleukin-2