TY - JOUR A1 - Simon, M. M. A1 - Nerz, G. A1 - Prester, M. A1 - Moll, Heidrun T1 - Immunoregulation by mouse T cell clones III. Cloned H-Y-specific cytotoxic T cells secrete a soluble mediator(s) that inhibits cytotoxic responses by acting on both Lyt-2\(^-\) and L3T4\(^-\)- lymphocytes N2 - In this study we report that cloned Thy-l +, L3T4-, Lyt-l-, Lyt-2+, H-Y-specific and H-2Db-restricted cytotoxic T ce11 lines (CTLL) when indueed by lectin or antigen secrete a soluble mediator(s) (SF) that inhibits proliferation and generation of cytotoxic lymphocytes (CTL) in mixed lymphocyte cultures (MLC). The biological activity was separable by gel filtration and appeared as a broad peak in the moleeular mass range between 10000 and 50000 kDa. It was found that the suppressive activity released by CTLL neither strictly correlates with their cytotoxic potential nor with their ability to produce immune interferon or Iymphotoxin. SF was shown to elicitits activity in an antigen-nonspeeific manner in that it suppressed the maturation of T lymphocytes responding to both, the appropriate H-Y antigen as weH as to unrelated H_2d alloantigens or to the hapten 2,4,6-trinitrophenyl (TNP). The effect of SF on CTL responses was most pronounced in early phases of primary or secondary MLC. When analyzed for its inhibitory activity on precursor ceHs in populations selected for either Lyt-2- or L3T4- lymphocytes, it was found that SF interfered with the maturation of both subsets. The inhibition of CTL responses elicited by SF could not be reversed by the addition of exogenous interleukin 2. The findtng that SF also inhi. bited the proliferation of some but not a11 antigen-dependent cloned T ceHs with helper or eytc'toxic potential provides evidence that the faetor also may regulate effector lymphl)cytes. In addition, the results support the assumption that SF exerts its effect direetly on the responder rather than the stimulator population, and demonstrate that the development of CTL from their preeursor eeHs is contro11ed at least in part by the eytotoxic effeetor cells themselves via a soluble factor(s) that interferes with distinct stages of T ce11 maturation. These findings again emphasize the expression of multiple functions by CTL and indieate their possible role du ring the course of an immune response by their capability to eliminate target cells and to secrete a soluble product(s) that mediates feedback contro!. KW - Infektionsbiologie Y1 - 1985 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-31625 ER - TY - JOUR A1 - Kramer, Michael D. A1 - Binninger, Linda A1 - Schirrmacher, Volker A1 - Moll, Heidrun A1 - Prester, Marlot A1 - Nerz, Gaby A1 - Simon, Markus M. T1 - Characterization and isolation of a trypsin-like serine protease from a long-term culture cytolytic t cell line andits expression by functionally distinct T cells N2 - No abstract available KW - Biologie Y1 - 1986 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-31636 ER - TY - JOUR A1 - Simon, Markus M. A1 - Moll, Heidrun A1 - Prester, Marlot A1 - Nerz, Gaby A1 - Eichmann, Klaus T1 - Immunoregulation by mouse T-cell clones. I. Suppression and amplification of cytotoxic responses by cloned H-Y-specific cytolytic T lymphocytes. N2 - H-Y-specific and H-2Db-restricted, Lyt-1 "2+ T-cell clones (CTLL) with graded specific cytotoxic activities on male C57BL/6 (B6) target cells (1E3, +++; 2C5, ++; 2A5, +, 3E6, ±) were tested for their capacity to inhibit the generation of H-Y-specific cytotoxic T lymphocytes (CTL) in vitro. Addition of irradiated lymphocytes of CTLL 1E3 and CTLL 3E6 but not those of CTLL 2A5 or CTLL 2C5 abolished the generation of CTL from in vivo primed H-Y-specific precursor cells (CTLP) when added to fresh mixed-lymphocyte cultures (MLC). Exogenous sources of T-cell growth factors (TCGF) did not overcome suppression. Rather the presence of TCGF resulted in a further enhancement of suppressive activities in CTLL 1E3 and 3E6 and the induction of similar activities in cells from CTLL 2A5 and 2C5, which by themselves were not inhibitory. Moreover when added to similar MLC on Day 1 instead of Day 0, only irradiated cells of CTLL 3E6 but not those of the other three CTLL were suppressive. Induction of suppressive activities in H-Y-specific CTLL was independent of the appropriate male stimulator cells since it was also observed in MLC induced by irrelevant antigens (H-2, trinitrophenol). Furthermore at low cell numbers, irradiated lymphocytes from any of the CTLL consistently enhanced CTL activities generated from H-Y-specific CTLP. This augmenting activity, which was not TCGF, could be transferred by soluble mediators present in antigen-sensitized CTLL cultures. Thus, these data indicate (i) that cytotoxic effector cells can function as suppressor cells in the generation of CTL, (ii) that the cytotoxic activity of cloned CTL does not correlate with their capacity to suppress CTL responses, (iii) that the inhibition of CTL responses by CTLL is not due to simple consumption of T-cell growth factors produced in MLC, and (iv) that different CTL clones may interfere with the generation of CTL at different stages of their maturation. Moreover, the experiments suggest an antigen-independent enhancement of suppression by the interaction of CTL with lymphokines. Together with the augmenting activity evoked by cloned CTL the data provide strong evidence for the expression of multiple immunological functions by one particular subset of T cells and suggest that cytotoxic effector cells can differentially regulate the maturation and/or clonal expression of their precursor cells. Y1 - 1984 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-30892 ER -