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T A Ferguson

Publications and source records attributed to T A Ferguson.

9 recordsLinked to original sources
PubMed1992

The wavelength of light governing intraocular immune reactions.

Injection of antigen into the anterior chamber of the eye results in the induction of suppressed systemic cell-mediated responses as measured by delayed-type hypersensitivity or contact hypersensitivity (CHS). Previous studies from the author's laboratories have determined that this response is governed by exposure of the eye to visible light during the initial intraocular encounter between T cells and antigen. To more fully understand the role of light, as well as to begin to understand the molecular mediators involved, the authors chose to explore the properties of light governing the effect. Neutral density filter were used to demonstrate that the minimum amount of light required to induce suppression of CHS following anterior chamber injection of antigen is 1-2 lux (lumens/meter2). With narrow band filters, the wavelengths responsible for suppression were shown to be 500-510 nm. The results show that the effect of light extends beyond the hapten-derivatized spleen cell system to other antigens placed in the anterior chamber of the eye. Studies also show that the retina and the pineal gland, two light absorbing structures, may not be involved. The results in this report show that light of very restricted wavelengths controls intraocular immune reactions.

Animals↗
PubMed1991

Two integrin-binding peptides abrogate T cell-mediated immune responses in vivo.

Two VLA proteins (or beta 1 integrins; originally called very late activation antigens) that bind to distinct determinants on fibronectin (FN) are increased on activated immune or memory T cells. VLA-4 binds to the peptide sequence Gly-Pro-Glu-Ile-Leu-Asp-Val-Pro-Ser-Thr (GPEILDVPST in single-letter code) on the alternatively spliced CS-1 form of FN, whereas VLA-5 binds to an Arg-Gly-Asp sequence found on all forms of FN. It has been proposed that the migration of immune T cells out of blood vessels and through connective tissue to a site of antigenic challenge is facilitated by the interaction of such integrins with matrix protein molecules. We have examined directly the role of T-cell integrins in vivo by using the well-characterized, T-cell-mediated contact hypersensitivity (CHS) response to the hapten trinitrochlorobenzene (TNCB). We demonstrate that the cells that transfer CHS to TNCB adhere to FN in the presence of Ca2+/Mg2+, and T-cell populations depleted of FN-adherent cells do not transfer immunity. We further show that TNCB-immune T cells treated with the synthetic peptides GPEILDVPST or Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP in single-letter code), ligands for VLA-4 and VLA-5, respectively, lose their ability to mediate this immune response in a murine model, whereas the control peptides Val-Ile-Pro-Asp-Leu-Thr-Glu-Ser-Pro-Gly and Gly-Arg-Gly-Glu-Ser-Pro have no effect. Neither GPEILDVPST nor GRGDSP significantly inhibited the proliferative response of TNCB-immune T cells in vitro. These data suggest that FN-binding integrins on T cells play a role in the localization of T cells to sites of antigenic challenge in tissue.

Amino Acid Sequence↗
PubMed1991

Inhibition of lymphocyte proliferation by resident ocular cells.

The mechanisms by which the eye maintains an immunosuppressive environment has been the subject of recent investigations. In this report we investigated the ability of resident ocular cells from the iris, choroid, and retina to inhibit lymphocyte responses in vitro. Our results demonstrate that single cell suspensions derived from iris and choroid to inhibit alloantigen induced lymphocyte proliferation. We show that this inhibition was mediated by soluble factors which are low (less than 10,000) and intermediate (10,000-30,000) molecular weight molecules. This capacity is limited to iris and choroid and is not demonstrable in cell preparations derived from the retina. We conclude from our studies that cells derived from iris and choroid are capable of regulating immune responses and suggest that these cells (or their soluble products) may play a role in the immunosuppressive environment of the eye.

Alkylating Agents↗
PubMed1989

The immune response and the eye. III. Anterior chamber-associated immune deviation can be adoptively transferred by serum.

After the anterior chamber (AC) injection of trinitrophenol-coupled (TNP) spleen cells, it is observed that systemic delayed-type hypersensitivity responses to TNP are inhibited by Ag-specific suppressor T cells. We recently reported that suppression is initiated by viable TNP-coupled T cells within the inoculum and upon further analysis we found that these cells have the surface phenotype of CD4+ Ts inducer cells. We report here that treatment of these TNP-T cells with cycloheximide or cytochalasin-B before to AC injection abolishes suppression, whereas treatment with 2000 rad radiation does not. This indicates that protein synthesis and secretion are required to initiate suppression but proliferation is not. Further, we demonstrate the adoptive transfer of suppression by serum of AC inoculated animals. Detection of the component in serum in adoptive transfer assays, however, requires removal of the spleen before AC injection. We establish that the material in serum is a Ts cell product (T suppressor-inducer factor) based on three criteria: it is Ag specific, genetically restricted, and reactive with a mAb that specifically identifies these molecules. These results suggest that the signal leaving the eye to induce suppression of delayed-type hypersensitivity is T cell derived and that molecules mediating immune regulation for this organ are made within the eye and transported via the serum to the spleen.

Animals↗
PubMed1989

An approach to the unification of suppressor T cell circuits: a simplified assay for the induction of suppression by T cell-derived, antigen-binding molecules (T-ABM).

A system is presented in which the in vitro response to sheep red blood cells (SRBC) can be regulated using antigenic determinants coupled to SRBC and T cell-derived antigen-binding molecules (T-ABM) directed against the coupled determinants. T suppressor-inducer factors (TsiF's) are composed of two molecules, one of which is a T-ABM and one which bears I-J determinants (I-J+ molecule). Using two purified T-ABM which have not previously been shown to have in vitro activity, we produced antigen-specific TsiF's which were capable of inducing the suppression of the anti-SRBC response. Suppression was found to require both the T-ABM and the I-J+ molecule, SRBC conjugated with the antigen for which the T-ABM was specific, and a population of Ly-2+ T cells in the culture. Two monoclonal TsiF (or TsF1) were demonstrated to induce suppression of the anti-SRBC response in this system, provided the relevant antigen was coupled to the SRBC in culture. The results are discussed in terms of the general functions of T-ABM in the immune system. This model will be useful in direct, experimental comparisons of the function of T-ABM and suppressor T cell factors under study in different systems and laboratories.

Animals↗
PubMed1986

Isolation and characterization of an antigen-specific suppressor inducer molecule from serum of hyperimmune mice by using a monoclonal antibody.

We have used a rat monoclonal antibody (mAb) (called 14-30) to affinity purify the antigen-binding chain of a suppressor inducer factor (TsiF-AB) from the serum of mice hyperimmune to heterologous erythrocytes. The TsiF-AB requires the addition of a second, antigen-nonspecific component for biologic activity as well as Lyt-2+ T cells in the assay culture. This mAb can be used to affinity purify suppressor inducer factor from a well-characterized TsiF but not suppressor effector factor (TseF) from culture supernatants. Binding of mAb 14-30 to TsiF is independent of the antigen specificity of the suppressor factor and of the strain of origin of the TsiF. The TsiF affinity purified from hyperimmune serum has an apparent m.w. of 68,000 by SDS-PAGE analysis. 2D gel analysis shows that the serum-derived TsiF has charge heterogeneity, all in the acid range.

Animals↗
PubMed1985

Isolation and characterization of a T suppressor factor by using a monoclonal antibody.

We have developed a monoclonal antibody to a T cell-derived suppressor factor (TsF) found in the serum of C57BL/6 mice hyperimmune to sheep red blood cells (SRBC). The antibody binds to the SRBC-specific TsF as well as to a TsF (TNP-TsF) from another system differing in both antigen specificity and MHC. It does not bind to unrelated proteins. The antibody inhibits the activity of the SRBC-specific TsF in vitro. By using the monoclonal anti-TsF, we can isolate sufficient quantities of TsF to demonstrate that it fulfills several properties that have been attributed to TsF, namely, MHC restriction, antigen specificity, and the requirement for a second chain. Also, the purified TsF gives a single 68,000 dalton band upon SDS-PAGE gel analysis under reducing conditions. We conclude, therefore, that we have a method of the isolation of pure TsF, as well as a probe for the genetic, biochemical, and biologic analysis of TsF.

Animals↗
PubMedDate not supplied

Suppressor T cells induced by epidermally applied hapten are located in bone marrow.

Mice painted epidermally with trinitrochlorobenzene (TNCB) develop delayed type dermal hypersensitivity within five days, however, subsequent immunization with TNP-syngeneic antigens (TNP-H2k) does not generate CTLs to the same antigens. These studies were undertaken to determine what prevents development of the CTL. We report here, that a suppressor cell for CTL generation is found in the bone marrow (BM) of TNCB-painted mice. This suppressor cell is not present in spleens or lymph nodes, but is readily detected by adoptive transfer of BM cells. The cell responsible for suppression is an Lyt2+ (CD8+) T cell. Further studies with two monoclonal antibodies (one directed to a T cell suppressor factor [mAb 14-12], and the other directed to a suppressor T cell inducer factor [mAb 14-30]), demonstrated that the suppression could be reversed by either antibody when they were given prior to epidermal hapten painting. However, when each mAb was administered to recipients of BM cells from hapten painted donors, only mAb 14-12 reversed suppression of CTL generation. Examination of the number of resident BM cells revealed that TNCB-sensitized mice had 35% more cells than normal controls. When cultured in vitro with inactivated, syngeneic TNP-thymocytes, BM from normal mice readily developed TNP-self specific CTL, whereas whole BM from hapten-painted mice did not. The inability to generate CTLs was found to be attributable to suppressor cells, since BM cells from hapten-painted mice prevented CTL development by splenic T cells in culture. BM cells from normal mice did not suppress CTL generation. Suppression in vitro was not overcome by the presence of exogenous IL-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗