TCR-independent induction of low responsiveness by chemically fixed cells in alloreactive CTL clones and its prevention through cognate cell-cell interaction.
We established BALB/c-derived CD8+ CTL clones D2-22 (V beta 6+), D2-23 (V beta 8+) and D2-24 (V beta 8+) specific for B10.D2 minor H antigen. D2-22 and D2-23 proliferated without producing IL-2 in response to X-ray-irradiated antigenic cells, Con A, aCD3, PMA and IL-2. Paraformaldehyde-fixed antigenic spleen cells neither induced proliferation in the presence of costimulatory cells nor inhibited responses to irradiated antigenic cells added simultaneously. Unlike the previously reported results with IL-2-producing CTL clones and Th1 clones, the fixed antigenic cells failed to induce antigen-specific unresponsiveness in these IL-2-non-producing CTL clones. Instead, the responsiveness of these clones to fresh stimulation was found to be reduced severely after 2 days in the culture added with either antigenic or syngeneic fixed cells. Induction of their antigen-nonspecific low responsiveness by the fixed cells was prevented by adding irradiated syngeneic cells into the culture or even by increasing the concentration of responder D2-23 cells. Close contact of D2-23 and irradiated syngeneic cells was required to prevent the reduction of the responsiveness, although this cognate cell-cell interaction could be replaced by exogenously added IL-2 or PMA. Cytolytic and tumor cell growth inhibitory activities of D2-23 were also reduced by incubation with the fixed cells, which was prevented by the addition of irradiated syngeneic cells. These findings showed the unique properties of IL-2-nonproducing CTL clones in signal requirements for maintaining normal responsiveness for proliferation and cytolytic activity.
Lwin
T
T
Department of Immunology, Nagoya University School of Medicine, Aichi, Japan.
Nakashima
I
I
Nagase
F
F
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D002450:Cell Communication / Q000187:drug effects / Q000528:radiation effects; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D005404:Fixatives; D005557:Formaldehyde / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011108:Polymers / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects
D005404:Fixatives; D007376:Interleukin-2; D007519:Isoantigens; D011108:Polymers; D011948:Receptors, Antigen, T-Cell; D005557:Formaldehyde; C003043:paraform