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L A Henderson

Publications and source records attributed to L A Henderson.

31 records · Page 2Linked to original sources
PubMed1988

Human immunodeficiency virus-induced cytotoxicity for CD8 cells from some normal donors and virus-specific induction of a suppressor factor.

Several aspects of human immunodeficiency virus (HIV)-induced pathology in vitro warrant close examination to ascertain their role in the development of disease in vivo. The ability of HIV to produce cytopathology of CD4 cells has been well documented, although the extent and mechanism(s) may be varied. Further, immune suppression by HIV envelope (env) is well documented in vitro, but its importance in vivo remains unknown and the role of other HIV components in immune suppression has not been examined. We have exposed peripheral blood mononuclear cells (PBMC) from normal donors to ultraviolet-irradiated HIV (uv-HIV) at concentrations similar to those found in AIDS patient serum and determined that in some normal donors (3/7) depletion of CD8 cells as well as CD4 cells is demonstrable. Abrogation of phytohemagglutinin (PHA)-induced proliferation by uv-HIV was also examined in the same normal donors. Immune suppression, unlike CD4 cell killing, does not require intact virus and occurs at physiologically relevant concentrations of HIV. Furthermore, PBMC exposed to uv-HIV in the presence of PHA produce a heat- and protease-labile suppressor factor(s) following removal of virus, whether or not they are reexposed to PHA. Our results suggest that cell killing may be a more broad event than previously described, including the killing of at least CD8 cells either directly or indirectly. In addition, suppressor factors produced following exposure of patient lymphocytes to agents that induce proliferation may exacerbate the development of opportunistic infection.

Animals↗
PubMed1988

Variations for susceptibilities to ultraviolet induced cellular inactivation and gene segregation among protoplast fusion hybrids of Candida albicans.

Hybrids of the naturally diploid, asexual and opportunistically pathogenic yeast, Candida albicans, can be obtained artificially by protoplast fusion. Evidence is presented that gene conversion and reciprocal recombination contribute to ultraviolet (UV)-induced segregations of heterozygous markers from both diploid and hybrid strains, and that hybrids also segregate through induced chromosome loss. Heterozygous diploid strains independently derived from the same wild-type diploid stock were alike in post-UV survival and segregational responses, and the organization of a four gene linkage group identified in diploids from the segregant products of reciprocal recombinations was transmitted intact to all hybrids from fusions between diploids of isogenic or nonisogenic backgrounds. However, hybrids arising independently from a given fusion cross differed significantly from each other in post-UV survival, absolute ability to segregate some parental markers, frequency of gene segregation, and proclivities for each of the three mechanisms of gene segregation. The bearings of the genetic backgrounds of parental strains and of growth temperatures during hybrid formation on each of these variables are described. The findings emphasize that awareness of the intrinsic heterogeneities of fusion hybrids is essential for reliable application of the protoplast fusion procedure to genetic analysis of C. albicans.

Candida albicans↗
PubMed1987

Transforming potential of a myc-containing variant of feline leukemia virus in vitro in early-passage feline cells.

We studied a naturally occurring variant of feline leukemia virus (FeLV) in which the oncogene myc has substituted for a portion of the viral structural genes (myc-FeLV). myc-FeLV was rescued by replication in the presence of FeLV as helper, and its biological activity was examined in early-passage feline cells in vitro. Infection of leukocytes from peripheral blood, spleen, or thymus, or of kitten fibroblasts did not immortalize these cells or alter them morphologically. Northern blot (RNA blot) analysis of virion RNA prepared from the supernatant of infected cells demonstrated the 8.2-kilobase genome of FeLV, but did not demonstrate the 5.0-kilobase genome of myc-FeLV. Apparently, the myc-FeLV genome was lost in the absence of the selective pressure of transformation. In contrast, infection of embryonic fibroblasts with myc-FeLV(FeLV) rendered these cells capable of greatly increased, if not infinite, proliferative potential. The cells were morphologically altered compared with controls and were only loosely adherent to the substrate. The cells failed to proliferate in semisolid medium and did not form tumors when inoculated subcutaneously into athymic mice. Blot analyses demonstrated the presence and expression of integrated proviral DNAs of both FeLV and myc-FeLV in these cells. They appear, then, to represent cells partially transformed by infection with myc-FeLV(FeLV). The action of feline v-myc in early-passage cells in vitro was compared to that of avian v-myc.

Animals↗
PubMed1985

Recognition of an Igh-linked histocompatibility antigen, H-40, on B-cell tumors by cytotoxic T lymphocytes.

This article reviews our data on H-40, a histocompatibility antigen controlled by a locus linked to Igh structural genes but telomeric to Tsu. The antigen is detected by rejection of H-40+ tumor cells in vivo and by the activity of H-2 restricted anti-H-40 cytotoxic T lymphocytes in vitro. H-40 is expressed on lipopolysaccharide stimulated B cells and B cell tumors that express surface(s) IgM and not on sIgM- tumors or other neoplastic cells. Its expression on the sIgM,D+ BALB/c (Igha, H-40a) derived leukemia, BCL1, prevents its transplantability across the Ig heavy chain (and H-40) barrier into C.B-20 (Ighb, H-40b) mice; whereas, BALB/c tumors that do not express H-40 can be transplanted into this allotype-congenic recipient. Although irradiated C.B-20 animals are susceptible to the BCL1 tumor, adoptive transfer of a mixture of Lyt-2+ and Lyt-2- effector cells (anti-H-40) from C.B-20 animals that have previously rejected BCL1 protect such recipients. However, the same effector cells will not protect irradiated BALB/c or (BALB/c X C.B-20)F1 recipients from this tumor. Since normal BALB/c sIg+ cells express H-40, either the effector cells are diverted from interacting with and destroying the tumor, or recognition of H-40 on non-tumor cells elicits a suppressor mechanism.

Animals↗
PubMed1985

Interaction of alpha 1 with alpha 2 region in class I MHC proteins contributes determinants recognized by antibodies and cytotoxic T cells.

The structure-function relationship of individual coding regions of class I mouse major histocompatibility complex proteins was studied by a combination of recombinant DNA, gene transfer techniques, and serologic and functional characterization. To examine the role of alpha 1 and alpha 2 regions in antibody and CTL recognition, the third exon of H-2Dd, Kd, and Ld transplantation antigen genes was replaced by the homologous coding region of the Qa-2-coded class I gene, Q6. We have chosen to carry out the exon shuffling experiments between these two different types of class I genes, because they are structurally similar and did not evolve to carry out identical functions. Therefore, it is less likely that the hybrid proteins will fortuitously recreate alpha 1-alpha 2 controlled functionally important determinants. The replacement of H-2 alpha 2 coding region with its Q6 counterpart had different effects on the expression of the three genes. The mutant H-2Dd gene transfected into L cells was expressed at high levels and retained several of the serologic determinants found on parental H-2Dd and Q6 domains. The serologic epitopes on the mutant H-2Kd-transfected cells were detectable at very low levels, whereas the product of the mutant H-2Ld gene could not be identified at all. Analysis of cells transfected with mutant H-2Dd gene with alloreactive and minor antigen(s)-restricted cytotoxic T cells indicated that the hybrid proteins lost the ability to be recognized by T cells. Our data suggest that cytotoxic T cells recognize conformational determinants composed of amino acids from alpha 1 and alpha 2 regions. Alternatively, it could be proposed that T cell recognition sites located in a single alpha 1 or alpha 2 protein region are susceptible to distortion upon alpha 1-alpha 2 interactions. Such susceptibility to conformational changes of the amino-terminal domain of transplantation antigens could be of functional importance for H-2-restricted antigen presentation.

Animals↗
PubMed1984

H-40, an antigen controlled by an Igh linked gene and recognized by cytotoxic T lymphocytes. I. Genetic analysis of H-40 and distribution of its product on B cell tumors.

C.B-20 ( Ighb ) mice challenged with BALB/c ( Igha ) spleen cells (or vice-versa) generate cytotoxic T lymphocytes (CTL) that recognize an antigen, H-40, controlled by an Igh-linked gene. The gene maps to the Igh-C region end of the Igh complex, telomeric to Tsu in the region of Pre-1. At least three alleles, a, b, and c, can be defined. Using a cold target competition assay, no polymorphism of the a allele was detected. Both surface Igh-5a positive and negative spleen cells from (C.B-20 X BALB/c)F1 animals express the a allele of the antigen, indicating that this gene is not allelically excluded. Recognition of the target antigen by CTL is restricted by the D-end of H-2d. The tissue distribution of H-40 was explored using both bulk-cultured and cloned CTL. The antigen is expressed on surface immunoglobulin positive (sIg+) cells and correlates with the expression of sIgM. This was determined by analysis of several B lymphomas as well as of other tumors that varied in their extent of expression of sIg. Four subclones of BCL1 were analyzed. Two of the subclones are sIg+ and express H-40, while two other subclones are sIg- and H-40-. Thus, these data define an Igh-linked gene, separate from immunoglobulin structural loci, that controls an antigen expressed on sIg+ cells. Possible mechanisms to account for this finding are discussed.

Alleles↗
PubMed1984

H-40, an antigen controlled by an Igh-linked gene and recognized by cytotoxic T lymphocytes. II. Recognition of H-40 as a tumor antigen in leukemic animals.

C.B-20 (Ighb) but not (C.B-20 X BALB/c)F1 mice reject BCL1, a sIg+ tumor that spontaneously arose in an Igh congenic BALB/c (Igha) mouse. C.B-20 immune T cells from mice immunized with either BCL1 or BALB/c splenocytes adoptively transfer tumor protection to sublethally irradiated C.B-20 but not BALB/c or (BALB/c X C.B-20)F1 mice. These data suggest that BALB/c and BCL1 share an antigen, which if present in the host prevents the immune cells from eradicating the tumor. The antigen is controlled by H-40, a gene that maps to the C end of the Igh complex, telomeric to Tsu and in the region of Pre-1. The ability of H-40 to act as a tumor antigen for other BALB/c tumors inoculated into C.B-20 hosts was investigated. H-40 did not elicit rejection of P1798 (T lymphoma), Meth A (fibrosarcoma), or MOPC-315 (alpha, lambda myeloma) tumor cells. C.B-20 mice that previously rejected BCL1, however, showed partial resistance to a low challenge dose of the MOPC-104E (mu, lambda myeloma) tumor. These data suggest that H-40 has a differential degree of expression on BALB/c tumor cells. The ability of the adoptively transferred cells to confer protection against BCL1 is abrogated by pretreatment of the cells with anti-Lyt-1 or anti-Lyt-2 antibodies. However, an admixture of anti-Lyt-1- and anti-Lyt-2-treated cells provided protection. These data, together with the results detected by cytotoxic T lymphocyte (CTL) activity in vitro, indicate that H-40 can serve as a target antigen for tumor rejection by CTL in allogeneic hosts. The implications of the results for allogeneic bone marrow transplantation into leukemic individuals who benefit from a graft vs leukemia effect are discussed.

Animals↗
PubMedDate not supplied

Modification of responses of Candida albicans to cisplatin by membrane damaging antimycotic agents.

The genotoxic, antineoplastic platinum coordination complex, cisplatin (cis-diamminedichloroplatinum (II], exists as a positively charged aquated complex in water solution and as a neutral, nonaquated complex in saline solution. Candida albicans exhibited greater susceptibilities to cellular inactivation and induction of mitotic recombination when treated with the aquated rather than the nonaquated drug. The differential in responses was expressed by cells grown after treatment at 37 degrees C or at 25 degrees C, a temperature which promotes recovery from DNA damages by the yeast generally. Studies with protoplasts established that cell wall components do not influence cellular reactions to either form of the drug. However, membrane damaging antimycotic agents markedly affected responses. Pretreatments with fungistatic ketoconazole or with miconazole, under fungistatic or fungicidal conditions, enhanced cellular resistance to inactivation by aquated cisplatin: the effect was more pronounced with post-cisplatin growth at 25 degrees C than 37 degrees C. Fungicidal pretreatments with amphotericin B or miconazole greatly increased susceptibilities of surviving cells to the lethal and recombinagenic effects of nonaquated cisplatin with post-cisplatin recovery at 25 degrees C or 37 degrees C. Possible mechanisms underlying these responses and their implications for stability of C. albicans populations in cancer patients undergoing therapy with cisplatin are discussed.

Amphotericin B↗