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Biomedical subjects

K V Sitz

Publications and source records attributed to K V Sitz.

9 recordsLinked to original sources
PubMed1997

Comparison of HIV-1 envelope-specific CD4+ T cell lines simultaneously established from peripheral blood mononuclear cells and lymph node biopsy in HIV-1-infected individuals.

HIV-1 envelope-specific CD4+ T cell lines were established simultaneously from PBMC and lymph node mononuclear cells of two HIV-1-infected patients. Three recombinant envelope proteins were used to establish the CD4+ T cell lines: gp160NL4-3, gp120IIIB, and gp120MN. Six T cell lines were established from the first patient, one for each Ag from each compartment, and four T cell lines, two per compartment, were established from the second patient. Each line was challenged with a panel of overlapping peptides spanning the entire gp120 sequence to define its T cell epitope specificity. The pattern of recognition for all the lines from any given patient was similar between compartments. Each patient had a different pattern of peptide recognition. TCR analysis showed a heterogeneous usage of Vbeta between lines with same peptide specificity and established from different compartments. These data suggest that the cellular immune response does not phenotypically vary between the peripheral blood and lymph node compartments, but demonstrates genotypic heterogeneity, showing possible redundancy of the immune response to HIV-1 gp160.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Expansion of restricted cellular immune responses to HIV-1 envelope by vaccination: IL-7 and IL-12 differentially augment cellular proliferative responses to HIV-1.

The failure of immune effector mechanisms to control HIV-1 infection has important consequences for the human host. In a randomized cohort of HIV-infected patients, there was striking in vitro restriction of the proliferative response to HIV-1 envelope protein (Env), gp160; only 34% of patients recognized Env. Therapeutic vaccination with recombinant gp160 or gp120 (rgp160, rgp120) reversed the restriction in vitro, with Env recognition rising to 81%. Peripheral blood mononuclear cells (PBMC) from HIV-infected vaccine recipients, placebo recipients, and seronegative volunteers were cultured with exogenous IL-7 or IL-12 and either tetanus toxoid (TT) or gp160. IL-7 significantly augmented proliferative responses to TT and gp160, whereas IL-12 only affected proliferation to gp160. IL-7, but not IL-12, increased the number of HIV-infected placebo recipients who recognized rgp160. IL-12 had its greatest effect in the induction of rgp160-specific responses from seronegative individuals. The data suggest that these two cytokines have differential activity in the relief of restricted cellular immunity to Env; the predominant effect of IL-7 is in individuals who have been primed by exposure to antigen, while the effect of IL-12 is most evident in seronegative, unprimed individuals. Modification of restricted proliferative responses to Env by vaccination or cytokines in vitro suggests that strategies incorporating IL-7 or IL-12 as adjuvants may selectively boost cellular reactivity to HIV-1.

AIDS Vaccines↗
PubMed1997

Delayed-type hypersensitivity skin testing using third variable loop peptides identifies T lymphocyte epitopes in human immunodeficiency virus-infected persons.

Cellular immune responses to human immunodeficiency virus type 1 (HIV-1) infection, particularly in vivo responses, have been difficult to study in large patient cohorts because of technical impediments. By use of small peptide fragments of the HIV-1 gp120 third variable loop, the CD4 T lymphocyte epitopes of 2 HIV-infected persons were mapped using a cutaneous delayed-type hypersensitivity (DTH) assay. The in vivo DTH responses correlated with epitopes previously identified in vitro using CD4 T lymphocyte lines. The ability to determine CD4 T lymphocyte epitopes in large cohorts of patients using this simple in vivo technique would provide important diagnostic and prognostic data regarding effective immunoregulation of HIV-1. This technique should have broad applicability in HIV vaccine development and in the investigation of other immune-mediated human diseases.

Amino Acid Sequence↗
PubMed1997

Mucosal immune responses in four distinct compartments of women infected with human immunodeficiency virus type 1: a comparison by site and correlation with clinical information.

Because mucosal immune responses may be important in protection against human immunodeficiency virus type 1 (HIV-1), HIV-1-specific immune responses at mucosal sites in natural infection were compared. Total antibody concentrations and HIV-1-specific binding antibody responses in four distinct mucosal sites and serum were assessed in 41 HIV-infected and 19 HIV-seronegative women. HIV-1 gp160-specific IgG responses were detected in >99% of mucosal samples in infected subjects, with the highest titers in genital secretions. HIV-1-specific IgA was detected in the majority of endocervical secretions (94%) and nasal washes (95%) but less often in vaginal washes (51%) and parotid saliva (38%). There was no significant correlation between mucosal immune response and most clinical factors. Based on methodologic considerations, frequencies of detection, and HIV-1-specific responses, nasal washes and genital secretions may each provide important measures of HIV-1-specific mucosal immune responses in infected women.

Adult↗
PubMed1996

CD4+ T-lymphocyte lines developed from HIV-1-seropositive patients recognize different epitopes within the V3 loop.

To define the epitopes present within the V3 loop sequence recognized by five HIV-1 envelope-specific T-cell lines, a panel of V3 LAI peptides bearing sequential truncations from both the N- and C-terminus was synthesized and tested for their ability to induce proliferation. Each individual T-cell line had a different pattern of response against the truncated V3 peptides, demonstrating the presence of a cluster of CD4+ T-cell epitopes within the V3 loop. To assess the ability of these envelope-specific T-cell lines to recognize and proliferate in response to V3 loops of different viral strains, they were tested against a panel of heterologous V3 loop peptides derived from different viral genotypes within and outside of HIV-1 clade B. There was no proliferative response against heterologous V3 loops by any of the lines, demonstrating that recognition of the V3 epitopes is highly strain specific. One of the defined epitopes was shown to elicit a cytotoxic response as well, suggesting the multifaceted role that the CD4+ T cell might play in HIV-1 disease.

Amino Acid Sequence↗
PubMed1995

Establishment and characterization of human immunodeficiency virus type 1 (HIV-1) envelope-specific CD4+ T lymphocyte lines from HIV-1-seropositive patients.

Human immunodeficiency virus type 1 (HIV-1) gp160-, gp120-, and tetanus toxoid-specific CD4+ T lymphocyte lines were developed from 11 HIV-1-seropositive volunteers enrolled in a vaccine therapy trial. Of the 20 HIV-1 envelope-specific T cell lines, 9 were challenged with a panel of overlapping peptides spanning the gp120LAI sequence. The most frequently recognized regions were amino acids 74-105 in the C1 region and 306-328 in the V3 region. When tested against a panel of divergent HIV-1 envelopes, 55% of the envelope-specific lines were able to recognize gp120MN, while only 22% recognized gp120SF2. Cytotoxicity testing with HIV-1 envelope antigen or peptides demonstrated killing by all 3 envelope-specific lines tested. Supernatants from 2 of 9 lines had high titers of p24 gag antigen, which did not seem to interfere with functional properties.

Amino Acid Sequence↗
PubMed1994

Consequences of stable transduction and antigen-inducible expression of the human interleukin-7 gene on tetanus-toxoid-specific T cells.

Interleukin-7 (IL-7) has previously been shown to increase antigen-specific immune responses; the effect of IL-7 on human antigen-specific T cell lines has not directly been addressed. A tetanus-toxoid (TT)-specific T cell line exhibited increased proliferation in the presence of exogenous IL-7, suggesting that IL-7 may be useful in the potentiation of immune responses to defined microbial antigens. Murine retroviral vectors encoding the human IL-7 gene and the neomycin phosphotransferase gene (neoR) were packaged into murine retroviral particles, and supernatants containing these retroviral vectors were used to infect a CD4+ lymphoblastoid cell line. Stable integration of the retroviral vector and constitutive expression of the IL-7 gene were observed. Successful IL-7 gene transduction into TT-specific T cells was also accomplished. Detection of neoR DNA sequences and expression of IL-7-specific mRNA increased with selection in geneticin. Production of IL-7 in these cells was induced by exposure to TT. Production of IL-4, IL-6, and interferon-gamma (IFN-gamma) was detected after antigenic stimulation; there was, however, no effect of IL-7 on the pattern or kinetics of cytokine production by these cells. Human IL-7 transduced cells showed greater proliferation to TT than control T cells, particularly at subthreshold TT concentrations. These dta imply that genetic modification of antigen-specific T cells may be a plausible strategy for the study and manipulation of the immune responses to microbial pathogens.

Animals↗
PubMed1987

Metastatic basal cell carcinoma in acquired immunodeficiency syndrome-related complex.

Basal cell carcinoma is a common neoplasm that rarely metastasizes. Metastatic basal cell carcinoma has been associated with a deficiency of cellular immunity. Patients with acquired immunodeficiency syndrome, at greater risk for specific neoplasms, may be at greater risk for basal cell carcinoma and subsequent metastasis. We report a case of metastatic basal cell carcinoma in a patient with acquired immunodeficiency syndrome-related complex.

AIDS-Related Complex↗