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J A Beatty

Publications and source records attributed to J A Beatty.

25 records · Page 2Linked to original sources
PubMed1996

A longitudinal study of feline immunodeficiency virus-specific cytotoxic T lymphocytes in experimentally infected cats, using antigen-specific induction.

The evolution of the virus-specific cytotoxic T-lymphocyte response in two cats experimentally infected with feline immunodeficiency virus (FIV) was monitored. Effector cells were derived from peripheral blood lymphocytes during the acute and chronic phases of infection (0 to 21 and 62 to 127 weeks, respectively) and from the spleen and lymph nodes at 127 weeks after infection. Lymphocytes were restimulated in vitro with paraformaldehyde-fixed, autologous lymphoblasts which had been infected with recombinant vaccinia viruses expressing FIV GAG or ENV proteins. Unstimulated lymphocytes were also used as effectors in some assays. 51Cr-labelled autologous skin fibroblasts infected with recombinant vaccinia viruses were used as targets. FIV GAG-specific cytotoxic precursors were detected in restimulated circulating lymphocytes during acute infection in both cats. The onset of this activity was as early as 2 weeks postinfection (p.i.) in one cat. From 62 weeks p.i. neither FIV GAG- nor ENV-specific precursors could be detected in the peripheral blood. However, at 127 weeks p.i., GAG- and ENV-specific cytotoxic precursors were detected in lymphocytes isolated from lymph nodes. The FIV-specific cytotoxic cells were predominantly major histocompatibility complex class I restricted. No cytotoxic activity was detected from unstimulated lymphocytes. These studies demonstrate the use of an assay system for dissecting the FIV-specific cytotoxic cell response and show that precursor cells appear in the circulation very early after infection and prior to a detectable antibody response. Our results also suggest that the persistent high-level circulating antiviral cytotoxic T-lymphocyte responses seen in human immunodeficiency virus-infected humans may not be a feature of FIV infections in cats.

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PubMed1995

Involvement of gag- and env-specific cytotoxic T lymphocytes in protective immunity to feline immunodeficiency virus.

Definition of the immunological mechanisms involved in protective immunity against lentiviral infections is crucial to the development of an effective vaccine. The induction of gag- and env-specific cell-mediated immune responses was studied in cats following vaccination with whole inactivated feline immunodeficiency virus (FIV). Cats were immunized by inoculation with three doses of paraformaldehyde-inactivated FIV, derived from the feline lymphoid cell line, FL-4, which is persistently infected with the Petaluma isolate of FIV. Autologous or allogeneic skin fibroblasts either infected with recombinant FIV gag- or env-vaccinia virus or pulsed with FIV env peptides were used as targets in chromium-51 release assays. Effector cells were fresh peripheral blood mononuclear cells. Following the third immunization, all vaccinated cats, but none of the control cats immunized with adjuvant alone, had detectable FIV env-specific lymphocytotoxicity in their peripheral blood. Two cats also exhibited gag-specific activity. There was no recognition of either allogeneic skin fibroblasts infected with recombinant vaccinia virus or autologous target cells infected with wild-type vaccinia virus, indicating the specificity and MHC-restricted nature of the response. Vaccinated cats, but not control cats, were protected from challenge with the homologous Petaluma isolate of FIV. Partial epitope mapping of the env-specific cytotoxic response was performed using overlapping 10-amino acid peptides from the env V3 domain of FIV. This response appeared to be directed at env peptide 1 (RAISSWKQRN) and env peptide 3 (QRNRWEWRPD), which lie adjacent to a beta-turn within the V3 domain.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1994

Induction of feline immunodeficiency virus-specific cytotoxic T cells in vivo with carrier-free synthetic peptide.

The role of cellular immunity in the establishment and progression of immunosuppressive lentivirus infection remains equivocal. To develop a model system with which these aspects of the host immune response can be studied experimentally, we examined the response of cats to a hybrid peptide containing predicted T-and B-cell epitopes from the gag and env genes of feline immunodeficiency virus (FIV). Cats were immunized with an unmodified 17-residue peptide incorporating residues 196 to 208 (from gag capsid protein p24) and 395 to 398 (from env glycoprotein gp120) of the FIV Glasgow-8 strain by using Quil A as an adjuvant. Virus-specific lymphocytotoxicity was measured by chromium-51 release assays. The target cells were autologous or allogeneic skin fibroblasts either infected with recombinant FIV gag vaccinia virus or pulsed with FIV peptides. Effector cells were either fresh peripheral blood mononuclear cells or T-cell lines stimulated with FIV peptides in vitro. Cytotoxic effector cells from immunized cats lysed autologous, but not allogeneic, target cells when they were either infected with recombinant FIV gag vaccinia virus or pulsed with synthetic peptides comprising residues 196 to 205 or 200 to 208 plus 395. Depletion of CD8+ T cells, from the effector cell population abrogated the lymphocytotoxicity. Immunized cats developed an antibody response to the 17-residue peptide immunogen and to recombinant p24. However, no antibodies which recognized smaller constituent peptides could be detected. This response correlated with peptide-induced T-cell proliferation in vitro. This study demonstrates that cytotoxic T lymphocytes specific for FIV can be induced following immunization with an unmodified short synthetic peptide and defines a system in which the protective or pathological role of such responses can be examined.

Amino Acid Sequence↗
PubMed1992

A recombinant feline immunodeficiency virus envelope fusion protein stimulates peripheral blood lymphocytes from naive cats to proliferate in vitro.

A region of feline immunodeficiency virus (FIV)/Glasgow-8 external envelope glycoprotein (env) incorporating the third and fourth variable regions (V3/V4) was cloned, inserted into the pGEX vector and expressed in Escherichia coli to yield milligram quantities of the recombinant polypeptide as a fusion protein with glutathione S-transferase. The fusion protein V3/V4GST was used in lymphocyte proliferation assays, where it consistently caused peripheral blood lymphocytes from naive cats to proliferate in a dose-dependent manner. Other FIV fusion proteins produced under identical conditions (V5GST and p24GST) and glutathione S-transferase alone did not cause proliferation in this system. The monoclonal antibody vpg15, which has been shown to block infection of susceptible cells in vitro, did not decrease the response to V3/V4GST. Human peripheral blood lymphocytes did not proliferate in response to V3/V4GST.

Amino Acid Sequence↗
PubMedDate not supplied

Antemortem diagnosis and treatment of toxoplasmosis in two cats on cyclosporin therapy.

Clinical toxoplasmosis was diagnosed antemortem in two cats being treated with therapeutic doses of cyclosporin. The diagnosis was made by detecting tachyzoites on cytological examination of bronchoalveolar lavage fluid from one case and pleural effusion from the other. Despite early diagnosis and aggressive treatment in both cases, only one cat survived. Reactivation of latent Toxoplasma gondii infection secondary to cyclosporin-induced immunosuppression was considered likely in both cases. The presence of respiratory signs in cats treated with cyclosporin should alert clinicians to the possibility of clinical toxoplasmosis. Consideration should be given to determining the serostatus of cats to T gondii prior to use of drugs which are potent inhibitors of cell mediated immunity, such as cyclosporin. Two cases of feline toxoplasmosis are presented.

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