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F Kiziroglu

Publications and source records attributed to F Kiziroglu.

5 recordsLinked to original sources
PubMed1994

Tolerance induction to multiple minor histoincompatible cells by activated B cells is associated with preferential activation of Th2 cells.

C3H/HeH or C57BL/6 mice were injected with resting or Escherichia coli lipopolysaccharide (LPS)-stimulated splenic B cells from adult B10.BR mice. Animals were grafted with tail skin grafts from B10.BR mice 36 hr later. Spleen cells were removed from these mice 7 days after grafting and challenged in tissue culture with irradiated B10.BR spleen cells or BALB/c cells. LPS blasts, but not naive B cells, induced an antigen-specific reduction in proliferation and IL-2 production from stimulated C3H/HeJ cells. The response obtained from C57BL/6 spleen responder cells was increased by this treatment. IL-4 production was either unchanged (C57BL/6) or enhanced (C3H/HeJ). Modification of the C3H/HeJ anti-B10.BR response by B blasts was not blocked by CTLA-4 Ig, although the increased response seen using MHC-incompatible (C57BL/6) spleen cells was inhibited by CTLA-4 Ig. B10.BR, but not BALB/c, skin graft survival in vivo was enhanced in C3H/HeJ recipients of B10.BR B blasts. In addition, in lymph nodes draining the graft site of C3H/HeJ mice injected with B10.BR LPS blasts, mRNA for IL-4 was detected by polymerase chain reaction. When similar studies were performed with B10.BR immune C3H/HeJ or C57BL/6 mice, no enhancement of graft survival in vivo, or decrease in proliferation/IL-2 production in vitro, was seen following prechallenge with B10.BR LPS blasts.

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PubMed1991

In vivo functional clonal deletion of recipient CD4+ T helper precursor cells that can recognize class II MHC on injected donor lymphoid cells.

Intravenous injection of semiallogeneic (C57BL/6XDBA/2)F1 lymphocytes into adult C57BL/6 recipient mice not only, as previously reported, reduces the recipients' cytotoxic T lymphocyte response in a subsequent in vitro mixed lymphocyte reaction against the injected cell type, but also reduces Th cell function in the same MLR. Thus lymphoid cells derived from the injected mice were greatly reduced in their ability to proliferate and to produce IL-2 in response to (C57BL/6XDBA/2)F1 stimulator cells in vitro, whereas third party responses were unaffected. This appears to be due to a reduction in the precursor frequency of IL-2-producing T lymphocytes specific for the injected cells as measured by limiting dilution analysis. Similar donor-specific reduction in the frequency of precursors of IL-2-producing cells was seen after i.v. injection of A.TL lymphocytes into A.TH recipients (differing at class II determinants I-A and I-E, but identical at K and D). Here there also appeared to be a functional clonal deletion of precursors of IL-2-producing Th cells, shown directly to be class II MHC reactive and CD4+. There is strong evidence that the reduction of class I-specific cytotoxic responses in the injected mice is a manifestation of donor cells that function as veto cells, i.e., that function as deletional APC that inactivate class I-reactive CTL precursors that recognize them. Our data in this study show that class II-specific Th responses are similarly reduced in the injected mice and suggest that CD4+ class II-reactive precursors of Th cells may be functionally inactivated in vivo by donor cells via a veto-like mechanism.

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PubMed1990

Direct effect of cyclosporin A on CD8+ T lymphocytes in a primary mixed lymphocyte reaction.

Cyclosporin A (CsA) blocks the development of cytotoxic T lymphocytes (CTL) in a primary mixed lymphocyte reaction (MLR) when added during the first few days of culture. We found that addition of recombinant IL-2 (rIL-2) or an IL-2-containing supernatant (2 degrees MLR SN) either alone or in combination was unable to reverse the suppression. Purified CD8+ responder cells were inhibited as effectively by CsA as unfractionated cells, suggesting that CsA has a direct, lymphokine-independent effect on CD8+ cells. The frequency of CTL precursors (CTLp) responding in a primary MLR was measured by limiting dilution in the presence and absence of CsA. Using either unfractionated cells or cell-sorter-purified CD8+ responder cells, no suppression was seen at very low cell numbers but increased markedly as the cell number per culture increased. These results imply that either a CD8+ regulatory/suppressor cell is being diluted out at low cell numbers, or that low cell-density culture conditions might override the inhibitory effects of CsA.

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PubMed1990

Effect of cyclosporine on secondary cytotoxic T lymphocyte responses.

Cyclosporine, a potent immunosuppressive agent, inhibits the development of the cytotoxic response in a secondary mixed lymphocyte reaction (MLR) in a dose-dependent manner. Exogenous lymphokines can partially overcome this inhibition. We present evidence that the CsA-resistant cells detected in these responses represent an activated population of memory CTL precursors that require only lymphokines for clonal growth and that kill targets of the original stimulator type only. Recombinant IL-4, when used at high concentrations, can support the generation of CTL in the presence of CsA during a secondary MLR response. The magnitude of the cytotoxic response though is far below the maximal levels achieved either by saturating quantities of rIL-2 or a combination of subsaturable quantities of rIL-2 and rIL-4.

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