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T A Ferguson

Publications and source records attributed to T A Ferguson.

At least 19 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↗
PubMed1988

Modulation of experimental allergic encephalomyelitis with anti-T suppressor factor antibodies.

mAb reactive with T suppressor factors (TsF) were used to alter the course of myelin basic protein-induced experimental allergic encephalomyelitis in (SJL/J x PL/J)F1 mice. In vivo administration of mAb 14-12, reactive with effector TsF, exacerbated the clinical expression of encephalomyelitis as evidenced by prolonged periods of total limb paralysis in affected animals. This aggravation of disease signs is probably related to the inhibition of effector Ts function by mAb 14-12 thus allowing T cell autoreactivity to proceed unchecked. Disease course was influenced more favorably by i.v. administration of mAb 14-30 reactive with a subset of inducer TsF. Ten days of treatment with this mAb resulted in a reduction in the incidence and severity of disease, noted as the development of minimal limb weakness but no paralysis in the majority of affected animals. Adoptive transfer experiments revealed the presence of Ag-specific Ts in mAb 14-30-treated mice that inhibited recipient Lyt-1+ responses to myelin basic protein, the immunizing autoantigen. Suppression by transferred Ts was revealed only by treatment of the donor population with anti-Lyt-1.2 plus C, however, indicating a role for contrasuppressor activity in the regulation of autoimmune T cell function. Results are considered relevant to the potential for immunotherapeutic management of multiple sclerosis in man.

Acute Disease↗
PubMed1988

The role of suppression in immunoregulation: in vivo analysis using a monoclonal antibody to T suppressor factors.

We have used a monoclonal antibody (mAb)-specific for murine T suppressor (Ts) cells (mAb 14-12) to study the role of T cells in tolerance and immunoregulation. We demonstrate that mAb 14-12 can block in vivo Ts cell activity in a variety of experimental systems. It prevents the induction of Ts cells induced by i.v. injection of the water-soluble hapten 2,4,6-trinitrobenzene sulfonic acid, and the protein antigen bovine serum albumin. When 14-12 mAb is given prior to the i.v. injection of trinitrophenyl-conjugated spleen cells (TNP-SC) it blocks the induction of Ts cells and sufficiently overcomes suppression so that TNP-SC is able to induce immunity. mAb 14-12 can convert nonresponder mice into responders for the Ir gene-controlled response to the random terpolymer L-glutamic acid60-L-alanine30-L-tyrosine 10 (GAT), and can substitute for cyclophosphamide in overcoming a suppressor barrier in the adoptive transfer of contact sensitivity. Administration of 14-12 mAb just prior to immunization results in the augmentation of contact sensitivity, antibody and plaque-forming cell responses. These results demonstrate the versatility of this reagent for the study of Ts cell activity.

Animals↗
PubMed1988

Infectious and noninfectious tolerance are blocked by a monoclonal antibody to T-suppressor factor.

Two forms of hapten-specific unresponsiveness have been demonstrated following intravenous (iv) injection of hapten-conjugated syngeneic spleen cell based on the nature of the antigen-presenting cell (APC): I-J+, I-A- APC have been shown to induce T-suppressor cells (Ts cells) which are demonstrated upon adoptive transfer, while I-J-, I-A+ APC induce a nontransferable tolerance. In this paper we report that a monoclonal antibody specific for T-suppressor effector cells and factors (14-12) can block the Ts cells induced by I-J+, I-A- APCs and the tolerance induced by I-J-, I-A+ APCs. In addition, it sufficiently overcomes suppression such that injection of TNP-spl iv induces immunity rather than suppression. We show that the I-A+, I-J- TNP-spl, which induce nontransferable tolerance upon iv injection, are the cells which induce immunity in 14-12-treated recipients. These results demonstrate that injection of I-J-, I-A+ APC does not lead to clonal deletion and the tolerance induced by the iv injection of both I-J+, I-A- and I-J-, I-A+ APC operate via Ts cells.

Animals↗
PubMed1988

Regulation of the systemic immune response by visible light and the eye.

The injection of certain antigens into the anterior chamber (AC) of the eye results in the induction of antigen-specific suppressor T cells (Ts cells), which inhibit systemic delayed-type hypersensitivity (DTH). We have previously shown that down-regulation by Ts cells after AC injection with 2,4,6-trinitrophenol (TNP)-coupled spleen cells (TNP-Spl) is initiated by the intraocular activation of Ts inducer cells. These cells activate T suppressor-effector cells in the spleen that are responsible for suppressed DTH. With dark- and light-reared mice (Balb/c), we show that visible light has a direct effect on the intraocular T cell reaction that leads to systemic suppression. Our results show that if light is prevented from reaching the eye by dark rearing, by placing light-reared animals in the dark after AC injection, or by closing the eyelids of light-reared animals after AC injection, Ts cells are not activated. We show that light is responsible for establishing conditions in the eye that cause the preferential activation of Ts cells. The intraocular conditions established by light are not developmentally mandated as is visual development, but can be eliminated in adult light-reared animals by placing them in the dark for 18 h after AC injection. These conditions can also be induced in adult dark-reared animals by returning them to the light for just over 24 h before AC injection. These studies have important implications for understanding intraocular immune responses and possibly for the treatment of eye disease.

Animals↗
PubMed1987

The immune response and the eye. I. The effects of monoclonal antibodies to T suppressor factors in anterior chamber-associated immune deviation (ACAID).

We report the effects of two monoclonal antibodies (mab) specific for murine T suppressor (Ts) factors (TsF) in anterior chamber (AC)-associated immune deviation (ACAID), as induced by AC inoculation of TNP-coupled syngeneic spleen cells (TNP-Spl). One mab (14-12) is specific for Ts effector factor and can block the induction of Ts cells in ACAID if given before or after AC injection of TNP-Spl. The other mab (14-30) is specific for Ts inducer factors and blocks suppression only after given after TNP-Spl. We also studied the surface phenotype of the Ts cells induced by AC injection of TNP-Spl. We show that at least two cells are required for the adoptive transfer of suppression in TNP-ACAID. One is Lyt-2+ and 14-12+, the other is I-J+. These Ts cells have the surface phenotype of Ts effector cells as seen in other systems. These results indicate that mab which bind TsF in other systems affect Ts cells in TNP-ACAID, and that the Ts cells induced in TNP-ACAID are only of the Ts effector type.

Animals↗
PubMed1987

The immune response and the eye. II. The nature of T suppressor cell induction in anterior chamber-associated immune deviation (ACAID).

We studied the cellular basis for the induction of Ts cells in anterior chamber (AC)-associated immune deviation (ACAID) by using TNP-modified syngeneic spleen cells (TNP-Spl). We demonstrate that the cells responsible for the induction of TNP-ACAID are non adherent, IA- T cells. This is in contrast to the antigen-presenting cells which induce suppression after the i.v. injection of TNP-Spl which are IA+/I-J+ adherent cells. Furthermore, two T cells within the TNP-Spl population are required to initiate suppression in TNP-ACAID: one is Lyt-1+, and I-J+, the other is Lyt-1+ and reactive with a monoclonal antibody, 14-30, which specifically identifies Ts inducer cells. The antigen specificity of ACAID resides in the 14-30+ T cell, and not the I-J+ cell. Although both cells must be viable to induce suppression, neither they (nor their products) must be in direct contact within the eye; one population may be in the right AC, the other in the left. Our results suggest that it is Ts inducer cells placed into the AC of the eye which initiate TNP-ACAID, and that these cells exit (or secrete Ts factors which exit) the eye to induce Ts effector cells in the spleen.

Animals↗
PubMed1987

A helper T cell clone produces an antigen-specific molecule (T-ABM) which functions in the induction of suppression.

Among Ly-1+,2-T cells there appears to be two independent modes of antigen recognition. Helper and cytotoxic Ly-1 T cells recognize antigen only in the context of I region products whereas regulatory T cells, such as T suppressor inducer cells, produce antigen-specific, antigen-binding molecules (T-ABM). These T-ABM often have been found to form a part of biologically active, antigen-specific regulatory factors. A number of environmental conditions effect whether a foreign antigen will produce a positive response leading to immunity or a negative one leading to tolerance. Many of the conditions which favor the induction of suppressor T cells simultaneously preclude the proper interaction of antigen presenting cells with helper T cells. This parallel led us to ask whether helper T cells perform at least two, apparently opposite functions: a) under conditions favoring immunity helper T cells produce lymphokines to activate immune effector cells, and b) under conditions favoring suppression they produce molecules which function in suppressor cell induction. Therefore, this question relates to the mechanisms by which an immune response is switched into either a positive (help) or negative (suppressive) track. In addition, it begins to address the relationship between the different modes of antigen recognition exhibited by helper T cells vs. T suppressor inducer cells (see above). To explore this problem we employed an antigen-specific, I-Ak restricted helper T cell clone as the purest available source of helper T cells. We presented antigen to the cloned T cells under conditions which favor suppression rather than help (for example, by ultraviolet irradiation of the antigen-presenting cells) and collected supernatants 48 hrs later. The supernatants were then examined for activity in a functional assay for antigen-specific suppressor factors. Our results indicate that under conditions favoring suppression, a T-ABM was produced which functioned in the antigen-specific induction of suppression in vitro. The T-ABM had the same antigen specificity as that exhibited by the helper T cell and was therefore probably derived from the clone. This observation introduces the possibility that the interaction between antigen-presenting cells and helper T cells is a crucial decision point in the immune response which can lead to either immunity or suppression. The latter would be achieved through the production, by helper T cells, of an antigen-specific component of T suppressor inducer factor (i.e., the T-ABM). The possible relationship between T-ABMs and the T cell receptor is discussed.

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↗
PubMed1986

Phenotypic similarity between T-cell antigen binding molecules.

T-cell antigen binding molecules (TABM) specific for trinitrophenol (TNP), oxazalone, azobenzenearsonate or sheep erythrocytes were purified by affinity to antigen, adsorption to monoclonal antibodies to antigen binding molecules or were synthesized by translation of immunopurified mRNA for TABM in vitro. These molecules and a T-cell line, BW5147, membrane protein bound by rabbit antibodies to TABM were radiolabeled by 125I, digested with Staphylococcus V8 protease, and peptides of the proteolytic digest were resolved by 2D-gel peptide mapping. Comparison of the peptide maps of these proteins and amino acid analysis of T-cell antigen binding molecules specific for TNP or sheep erythrocytes indicate similarities and distinctions suggesting variable and constant domains in these molecules.

Amino Acids↗
PubMed1985

A burn induced Ly-2 suppressor T cell lowers resistance to bacterial infection.

Suppressor T cell activity after major burn injury in a murine model has been well characterized. Suppressor cells have also been demonstrated in patients after major burn, and suppressor cell activity has been temporally correlated with septic episodes. A splenic Ly-2 T suppressor effector (Tse) cell appearing 7 days after a 30% full thickness burn has been identified in a murine model. A rat monoclonal antibody (14-8c3-12) directed against a factor produced by the Tse cell (Tsef) can enhance depressed in vitro mixed lymphocyte reaction (MLR) responses of Day 7 burn spleen cells without enhancing control spleen cell activity. Additionally, 14-8c3-12 can block the suppressive effect of these burn T cells on normal T cells. A cecal ligation and puncture (CLP) model using a 25-gauge needle (LD15) was used to assess the contribution of burn T cells to post-CLP mortality. Normal spleen cells injected into syngeneic recipients followed by CLP did not affect mortality (13%). Burn spleen cells injected into normal recipients enhanced mortality sixfold (90%) after CLP. The effect could be reversed by removing Ly-2 T cells (30% mortality) but not Ly-1 T cells (100% mortality) prior to cell transfer. Simultaneous injection of 14-8c3-12 antibody with burn T cells reduced mortality after CLP significantly (20%). Injection of 14-8c3-12 did not improve survival after CLP in control animals not injected with burn T cells (20%). Ly-2 T suppressor effector cells found in the spleens of mice 7 days postburn enhance the lethality of a purely bacterial septic challenge. A monoclonal antibody to the Tsef can reverse this effect in vivo.

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↗