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K K Klyczek

Publications and source records attributed to K K Klyczek.

15 recordsLinked to original sources
PubMed1992

Introduction of the H-2Dk gene into a class I-negative tumor cell line confers interferon-gamma inducibility upon the silent endogenous H-2Kk gene.

Kgv cells do not constitutively express class I mRNA or protein. Interferon (IFN)-gamma, but not IFN-alpha/beta, induces H-2Dk expression. IFN does not induce H-2Kk expression. We examined constitutive and IFN-inducible class I expression on Kgv cells stably transfected with genomic clones of H-2Kk or H-2Dk and on somatic cell hybrid lines constructed between Kgv cells and constitutively class I-positive cells of a distinguishable H-2 haplotype. Our results suggest that both the lack of constitutive class I expression and the inability of IFN-alpha/beta to induce class I expression on Kgv cells are primarily due to cis-regulatory mechanisms. However, stable introduction of the H-2Dk gene into Kgv cells conferred IFN-gamma inducibility upon the silent endogenous H-2Kk gene. Therefore, the failure of IFN-gamma to induce H-2Kk expression on Kgv cells is due, at least in part, to a trans-regulatory mechanism.

Animals↗
PubMed1992

Interferon-alpha/beta, pentoxifylline, and caffeine synergize with interferon-gamma to induce major histocompatibility complex class I expression on a constitutively class I-negative murine tumor cell line.

The constitutively class I-negative tumor cell line, Kgv, expresses H-2Dk in response to interferon-gamma (IFN-gamma), but not in response to IFN-alpha/beta, tumor necrosis factor, or lymphotoxin. H-2Dk expression was not induced on Kgv cells by the methylxanthines, pentoxifylline (PTX) and caffeine, which modulate class I expression on cells that constitutively express class I molecules. Treatment of Kgv cells with either IFN-alpha/beta, PTX, caffeine, or dibutyryl cAMP and a concentration of IFN-gamma insufficient by itself to induce Dk expression resulted in the induction of Dk expression. Since PTX and caffeine are cAMP-specific phosphodiesterase inhibitors, it is possible that the effects of PTX, caffeine, and dibutyryl cAMP involve a cAMP-dependent mechanism. We conclude that concentrations of IFN-gamma insufficient to induce Dk expression on Kgv cells may be capable of rendering the Dk gene responsive to signals that, in the absence of IFN-gamma treatment, have no effect on Dk expression.

Animals↗
PubMed1992

Altered macrophage antigen-presenting cell function following Friend leukemia virus infection.

To investigate the mechanism by which Friend leukemia virus (FV) causes immunosuppression, the ability of peritoneal macrophages to mediate antigen-specific T-cell activation following FV infection was examined. Decreased IL-2 production was observed when antigen-primed T cells were cultured with antigen-pulsed macrophages from mice infected with FV, compared to T cells cultured with macrophages from control mice. Macrophages from FV-infected mice demonstrated decreased phagocytic and pinocytic activity, suggesting that antigen uptake may be impaired in these cells. In addition, FV-infected mice had decreased numbers of MHC class II positive macrophages compared to uninfected controls, as measured by immunofluorescence. The alterations in antigen uptake and class II expression observed in macrophages from FV-infected mice may be the result of infection of these cells by FV, which was demonstrated by in situ hybridization using a FV-specific probe. The ability of FV to infect and modulate the functions of macrophages may account, at least in part, for the immunosuppression observed in FV-infected mice.

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PubMed1990

Effect of Friend leukemia virus infection on susceptibility to Candida albicans.

Previous studies have demonstrated that Friend leukemia virus (FLV) induces a profound immunosuppression in susceptible mice. The studies described in this report indicate that mice infected with FLV have an increased susceptibility to subsequent infection with the opportunistic pathogen Candida albicans, as measured by increased numbers of C. albicans CFU in the kidneys of FLV-infected mice relative to uninfected controls. Experiments in which the NB-tropic and N-tropic strains of FLV were used suggest that virus replication or the resulting virus burden may be important in the observed increased susceptibility to C. albicans. Since neutrophils are believed to be important in the response of mice to systemic Candida infections, the effect of FLV infection on neutrophil candidacidal activity was investigated. The percentage of neutrophils present in unfractionated Proteose Peptone-elicited peritoneal exudates of mice infected with FLV for 14 days was significantly lower than in uninfected control mice or mice infected with FLV for 6 or 10 days. When neutrophils from FLV-infected and control mice were purified, adjusted to equal concentrations, and tested for in vitro candidacidal activity, neutrophils from mice infected with FLV for 14 days were deficient in their ability to kill C. albicans relative to normal controls and mice infected with FLV for 6 or 10 days. Addition of normal mouse serum increased killing in all groups but did not restore candidacidal activity of neutrophils from mice infected with FLV for 14 days to levels of control neutrophils or neutrophils from mice infected for 6 or 10 days with the virus. These results suggest a defect in neutrophil function, at the later stages of FLV infection, involving in vitro candidacidal activity. In addition, neutrophils from FLV-infected mice may be deficient in in vivo chemotactic activity. These defects in neutrophil function could account, at least in part, for the observed increased susceptibility of FLV-infected mice to C. albicans.

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PubMed1989

Novel class I-like molecule expressed on a murine leukemia virus-transformed cell line.

A retrovirus-induced tumor cell line, which expresses no H-2K or H-2D class I molecules, appears to express a tumor-specific transplantation antigen which induces tumor rejection in vivo and cytotoxic T lymphocyte generation in vitro without prior immunization and thus resembles class I molecules. In addition, although these tumor cells express no detectable class I molecules, they do express beta 2 microglobulin and a 55- to 60-kDa beta 2 microglobulin-associated protein. Northern analysis demonstrated that these cells express no RNA hybridizing to class I probes, suggesting that neither the tumor-specific transplantation antigen nor the beta 2 microglobulin-associated protein, if these are different, are encoded by known class I genes.

AKR murine leukemia virus↗
PubMed1989

In vivo generation of antigenic variants of murine retroviruses.

Inoculation of adult BALB/c-H-2k (BALB.K) mice with both Gross murine leukemia virus (GV) and a biological clone derived from this virus resulted in the recovery of variant viruses which differ from GV with respect to the expression of specific epitopes associated with the env gene product, gp70. The loss of these epitopes correlated with the failure of antiserum raised in BALB.K mice against GV to neutralize variant virus although this antiserum neutralized GV. In contrast, BALB/c-H-2b (BALB.B) mice, immunized with GV, produced antibodies which neutralized both GV and the variant virus, indicating that BALB.B mice respond to epitopes distinct from those recognized by BALB.K mice. These results suggest that the selection of variant viruses resulting from in vivo passage may be related to the immunoselective pressures exerted in mice which express particular alleles of certain major histocompatibility complex (MHC)-linked genes.

AKR murine leukemia virus↗
PubMed1987

Interferon-gamma, interferon-alpha/beta, and tumor necrosis factor differentially affect major histocompatibility complex class I expression in murine leukemia virus-induced tumor cell lines.

Tumor cell lines induced by Gross murine leukemia virus were examined for cell-surface major histocompatibility complex class I expression. Three of five cell lines constitutively express H-2K and H-2D class I protein. Culturing these cells with interferon (IFN)-gamma, IFN-alpha/beta, or tumor necrosis factor increases both K and D expression in these cell lines. Two of five tumor cell lines express no class I proteins by fluorescence-activated cell sorter analysis, specific immunoprecipitation, and specific hybridization in Northern analysis. Treatment with IFN-gamma induces D, but not K protein expression in one of these cell lines. IFN-alpha/beta and tumor necrosis factor induce neither D nor K expression in this cell line. Thus, these two cytokines appear to have different mechanisms of action than IFN-gamma for altering class I expression. The other class I-negative tumor cell line does not express either K or D proteins under any conditions tested. All five cell lines express beta 2-microglobulin; this expression is increased by IFN-gamma treatment even in cell lines which do not express class I heavy chain. The results of this study demonstrate that 1) different tumor cell lines demonstrate variations in class I gene regulation, and 2) differences in regulation between class I genes may occur within a single cell line.

AKR murine leukemia virus↗
PubMed1986

Antigenic changes in gp70 associated with the adult variant of Gross murine leukemia virus, WB91.

Gross murine leukemia virus (GV) is not leukemogenic in adult mice whereas a variant of GV, WB91, is highly leukemogenic regardless of the age of the inoculated animal. FACS and SDS-PAGE analysis have demonstrated that these viruses differ at least with respect to the env-encoded gp70 molecule. FACS analysis of virus infected or virus transformed cells with a type specific monoclonal antibody (mAb #55) indicated a difference in determinants associated with gp70 expressed by the two viruses. Rat antisera raised against GV- or WB91-induced tumor cells demonstrated that there were no crossreactive determinants between the gp70 molecules expressed on these tumor cells as recognized by the rat antisera. This difference in the gp70 molecules encoded by WB91 and GV may account for the ability of the WB91 virus to induce leukemia in adult mice, possibly by affecting the immunogenicity of the virus.

AKR murine leukemia virus↗
PubMed1985

The I-J glycoprotein: genetic control, biochemistry, and function.

The I-J molecule is a mannosylated protein expressed early in T cell ontogeny in partially shielded form, later fully exposed on an activated T cell subset. Others determined a 25-30,000 molecular weight for cellular (Kumagai et al. 1984) and secreted forms (Taniguchi et al. 1984). Both the cell membrane and secreted types seem to govern genetically-restricted interactions completing suppressor cell circuits. The soluble I-J polypeptide has no antigen-binding site, but associates with an antigen-binding chain via disulfide bonding (Taniguchi et al. 1984, Lei et al. 1983). Similarly, evidence suggests that cellular I-J molecules are part of or proximal to T cell antigen receptor complexes (Fig. 4). At least two genes control T cell I-Jk expression, one apparently in I-E, another on chromosome 4. Undiscovered loci may also participate. Since I-J+ T cells do not transcribe I-region DNA, the I-E gene must be an untranscribed regulatory element in T cells or a protein translated in the host environment. If in the host environment, it probably does not function enzymatically to form T cell I-J epitopes; removed from the host, T cells biosynthesize complete I-J determinants. Host I-E gene products may regulate I-J expression in an early T cell maturation step. For example, the E alpha E beta proteins of thymic macrophages and epithelial cells may drive the expansion of T cells with E alpha E beta-complementary receptors encoded by I-J genes outside H-2. Genetic control of this self receptor would then apparently map to the selective ligand gene, I-E, as well as the I-J structural gene elsewhere (Klyczek et al. 1984b). This attractive theory, proposed in its original form by Jerne (1971) and later by Schrader (1979), has received significant support. Definitive proof must await further experimentation.

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PubMed1984

T cell surface I-J glycoprotein. Concerted action of chromosome-4 and -17 genes forms an epitope dependent on alpha-D-mannosyl residues.

Two genes acting in concert control murine T cell I-Jk expression. We determined I-Jk expression with I-Jk--specific monoclonal antibodies WF8 .C12.8 and five others produced in our laboratory in a cytotoxicity assay. Previous experiments established that an H-2k gene and a chromosome 4 gene, Jt , regulate I-Jk expression. We show here that B10. HTT and B10.S( 9R ) do not differ at the H-2k locus required for I-Jk expression. Rather B10. HTT , like B10.A(3R), lacks some important non--H-2 gene (possibly Jt ). The intra--H-2k I-J--controlling locus maps to the right of the I-A subregion. The I-Jk determinant involves a carbohydrate structure associated with protein; inhibiting either protein synthesis or glycosylation prevents T cell I-Jk reexpression after proteolytic removal. Treatment with alpha-mannosidase destroys I-Jk determinants, implicating terminal alpha-D-mannosyl residues in the I-Jk epitope. Models for H-2 and Jt control of I-J expression are discussed.

Animals↗
PubMed1984

Chromosome 4 Jt gene controls murine T cell surface I-J expression.

Data are presented suggesting a resolution to the paradox concerning the murine response subregion I-J, which encodes a suppressor T cell marker. The controversy arose when sequences corresponding to I-J DNA were not found in the central immune response region described by immunogeneticists. New evidence is presented that T cell surface I-J expression results from the action of at least two complementing genes. One gene is within the H-2 region on chromosome 17; the second gene, termed Jt, is on chromosome 4. The two recombinant mouse strains B10.A(3R) and B10.A(5R) originally used to define the I-J subregion apparently differ not within the H-2 region but elsewhere.

Animals↗
PubMed1984

T cell determinant mapping between K and I-A with I-region properties.

We investigated genes in the chromosomal segment between K and I-A. Recombination in strains AQR and A.TL previously established the right-hand K region and left-hand I-A subregion boundaries. This report provides evidence that strains AQR and A.TL differ in their intra-I-region crossover points; AQR has k haplotype genes between K and I-A which A.TL lacks. Using three different strain combinations, we produced antibodies specific for a T lymphocyte determinant, Iat.W41, encoded by genes in the Kk to I-Ak interval. Like A.TL, B10.MBR (an intra-I-region recombinant) lacks the Iat.W41-controlling gene. Immunofluorescence analysis and a cytotoxicity assay detected Iat.W41 determinants on mature T lymphocyte subset; thymocytes, bone marrow cells, B cells and macrophages do not express this specificity. Iat.W41-bearing lymphocytes display the Thy-1.2 antigen, but not Ly-1 or Ly-2 determinants. Iat.W41 expression is independent of non-H-2 genes. In addition to a strong mixed leukocyte reaction, genes between K and I-A contribute to a graft-versus-host reaction. The Iat.W41-controlling locus appears distinct from previously identified I-A loci.

Animals↗
PubMed1984

I-A-controlled T cell molecules: protease sensitivity.

An I-A subregion-controlled structure (I-At) characterizes some helper T cells and augmenting factors. This epitope is associated with a glycoprotein. Extended trypsin digestion removed the determinant; tunicamycin blocked its reexpression. In contrast, limited trypsinization increased the number of I-At-bearing peripheral T cells from 17 to 35%. The I-At molecule density on cells expressing this structure did not change measurably with limited enzyme treatment. Rather, some previously negative T cells (20%) expressed the epitope after mild proteolysis. A third T cell subset (60%) expressed no I-At molecules regardless of enzyme treatment. We conclude that the I-At molecule is shielded by trypsin-labile material on some T cells, whereas on others it is fully exposed. The transition from a shielded to an exposed configuration may correlate with T cell activation. Cycloheximide inhibited the biosynthesis of both the I-At molecule and the shielding substance by T cells. Unlike I-A-controlled T cell structures, B cell I-A-encoded molecules are neither shielded nor trypsin labile. The relationship between I region-controlled T cell and B cell molecules is discussed.

Animals↗
PubMed1983

Enhancement of murine T cell I-J expression by limited proteolysis.

I-J-encoded structures on peripheral T cells and thymocytes appear normally to be blocked or shielded by material that is susceptible to proteolysis. Limited proteolysis with trypsin, papain, pronase, or chymotrypsin increased the number of peripheral T cells and thymocytes lysed by anti-I-Jk serum and complement. Proteolysis did not induce I-Jk expression on B cells or on negative strain T cells. Increased lysis was enzyme concentration and time dependent and was not due to increased susceptibility of protease-treated cells to lysis by antibody plus complement; proteolysis rendered T cells and thymocytes less susceptible to lysis by anti-H-2Kk, anti-H-2Dd, and anti-Lyt-2 antibodies. Absorption experiments showed that I-Jk determinant density was increased in the protease-treated T cell population. The I-Jk determinants detected are proteins or glycoproteins; extended proteolysis removed these molecules from the T cell surface. Treatment of T cells or thymocytes with activated macrophage culture supernatant containing proteolytic activity produced a small but reproducible increase in I-Jk expression. Proteolysis of lymphocyte membranes, possibly mediated by macrophages, may have a role in cellular differentiation and immune activation.

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