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Biomedical subjects

R E Click

Publications and source records attributed to R E Click.

At least 19 recordsLinked to original sources
PubMed1994

Rejection of rat skin xenografts by either murine CD4 or CD8 T cells.

Although xenografts can be rejected by humoral or cellular mechanisms, the relative contribution of each remains unknown for any given recipient-donor combination. Moreover, the cells involved in cell-mediated events, as well as the mechanisms by which these cells recognize xenoantigens, remain controversial. It would be advantageous to have a model in which either, as well as various parts of either, could be investigated in the absence of the other, as well as in the absence of events taking place during organ engraftment. In the present report, rejection of rat skin xenografts was monitored after adoptive transfer of unique populations of highly purified lymphoid cells to previously transplanted immunodeficient C.B17 Scid/Scid mice. Purified T cells and, unexpectedly, purified CD4+ T cells alone and purified CD8+ T cells alone rejected rat xenografts. Alternatives that may explain these findings are discussed.

Animals↗
PubMed1992

Functional alterations of swine peripheral blood mononuclear cells by methadone.

In vitro exposure of the synthetic opiate drug methadone allowed evaluation of putative immunomodulatory activities of swine peripheral blood mononuclear cells. Respiratory burst, an index of microbicidal activity, was suppressed by methadone in a dose-dependent manner following exposure for 48 h. The suppression was blocked by the opiate antagonist naloxone. Another macrophage function phagosome-lysosome fusion was impaired by exposure to methadone. A primary lymphocyte-mediated function natural killer cell activity was also affected. In contrast, the macrophage function antibody-mediated phagocytosis was not affected. Because the functions affected by methadone are critical to host defenses against pathogenic organisms, our findings suggest that opiate-mediated immunomodulation merits further study. Moreover, our studies suggest that swine may provide an ideal model for the investigation of opiate-mediated suppression of immune cell functions.

Animals↗
PubMed1990

Unconventional lymphocytes involved in rejection of xenogeneic heart grafts.

In this report, the efficacy of cyclosporine A and two monoclonal antibodies, anti-L3T4 and anti-Lyt-2.2, was assessed on first-set rejection of cardiac xenografts. Neither cyclosporine nor anti-Lyt-2.2 monoclonal antibody prolonged the survival of heart xenografts. Anti-L3T4 enhanced acceptance of rat hearts transplanted to C57BL/6 mice 5-fold relative to that observed in control recipients; it did not, however, prolong acceptance of hamster hearts transplanted to mice. Histologic analysis indicated that the cellular infiltrate within rejected hearts was composed of greater than 95% lymphocytes; of these, greater than 99% were Thy-1- and sIg-. These results suggest that rejection of xenogeneic hearts is mediated by unconventional lymphoid cells. This is discussed in the context of whether rejection of allografts and xenografts occur by similar or dissimilar mechanisms.

Animals↗
PubMed1989

Multi-gene/allele control of Mlsb of CBA/H.

Festenstein originally described the Mls locus as a single dominant autosomal gene with four alleles which mapped in the 13th linkage group of chromosome 1. We subsequently presented evidence indicating that the mixed leukocyte reaction (MLR) stimulatory products of DBA/2 and CBA/J were controlled by two independently segregating Mls loci and that Mls of C3H was in fact a composite of three independently segregating loci. Recently, Mlsd of CBA/J was shown to be composed of Mlsa of AKR and a product on C3H, which was presumed to be Mlsc. Based on strain distributions, this product cannot be encoded by the Mlsc originally defined by Festenstein. In the present report, three Mls specificities of CBA/H (Mlsb) are defined. Based on the strain distribution, we postulate that these specificities are controlled by three loci, three alleles/locus, or by some combination of the preceding two possibilities.

Alleles↗
PubMed1988

Multigene control of Mlsc.

Festenstein originally described the Mls locus as a single dominant autosomal gene with four alleles which mapped in the 13th linkage group of chromosome 1. We subsequently presented evidence which indicated that the mixed leukocyte reaction stimulatory products of DBA/2 and CBA/J were controlled by two independently segregating Mls loci. Recently, Mlsd of CBA/J was shown to be composed of Mlsa of AKR and Mlsc of C3H. In the present report, classic segregation data is presented which indicates that Mlsc of C3H is controlled by three independently segregating loci. As defined by stimulatory patterns of numerous cell lines, we postulate the following: either one of the loci is shared with BALB.K, CE, C58, and partially with MA/MyJ, one is shared with CBA/H and CBA/J, and one is shared with BALB.K, CBA/J, and partially with CE; or the groups of shared determinants are controlled by different alleles of unique loci (or locus). In any event, Mlsc appears to be composed of at least three independently segregating loci; the number of alleles/locus is being investigated. In addition, C3H was stimulated by BALB.K (both were recently postulated to be Mlsc); this epitope was shared with CBA/J, CBA/H, AKR/Cum, Ma/MyJ, and C58/J.

Animals↗
PubMed1987

Nonresponsiveness to Mlsd in F1 hybrid mice carrying Mlsa and Mlsc genes.

Neither the biological function nor a basic understanding of the enigmatic chromosome 1-encoded Mls locus of the mouse has yet been uncovered despite extensive investigations. The present report is a continuation of our genetic analyses of the Mls locus in an attempt to better define the system. Data presented here indicate that in contrast to cells of mice expressing either the Mlsa or Mlsc allele which respond in mixed leukocyte reactions to cells expressing the Mlsd allelic products, cells from (Mlsa X Mlsc)F1-hybrid mice do not. In addition, the nonresponder phenotype appears to segregate as a single autosomal genetic system in backcross animals. These findings fail to support two recently advanced hypotheses: first, that the Mls locus is nonpolymorphic, or second, that the Mls locus controls differential expression of Ia antigenic determinants. Although the mechanism by which a (responder X responder) converts to a nonresponder remains unknown, three models involving gene complementation are discussed.

Animals↗
PubMed1985

Complexity of minor histocompatibility loci.

Allografts can be rejected as a result of major histocompatibility antigen disparity or as a result of differences at any of a number of minor histocompatibility antigens. In many cases, rejection due to multiple minor histoincompatibility is as difficult to control as that induced by major histoincompatibility. Although an understanding of the molecular, biochemical, and functional parameters of the major histocompatibility loci and their products is increasing at an exponential rate, little is known about these same facets of minor histocompatibility loci and their products. It is generally accepted that minor histocompatibility loci in the murine model have a degree of polymorphism similar to that of H-2K or H-2D. This conclusion was based on typing alleles by the classic F1-skin graft test. Based on these allelic assignments, numerous unexpected findings of CTL specificity were made. Therefore, a systematic analysis was made comparing CTL specificity, F1-complementation, and allograft rejection. Based on these three parameters, the data presented using strains of mice that were bred to, and therefore presumed to, differ only at H-3 indicate that the antigen disparity of these congenic strains and the parental B10 strain as defined by CTL specificity and skin graft rejection is much more complex than originally described. One especially interesting chromosomal region is H-3/beta 2-microglobulin in the fifth linkage group of chromosome 2. Using CTL, ten specificities are defined, three of which appear to be specific for beta 2-microglobulin-A, -B, and -C. These findings raise the question of whether any minor histocompatibility locus is polymorphic or is instead a composite of multiple minor H-loci which are masquerading as a single locus.

Alleles↗
PubMed1985

CTL and serologically defined antigens of B2m,H-3 region.

The antigens of the B2m,H-3 region of 13 chromosome 2 congenic strains and seven inbred strains have been studied by using CML and serologic techniques. Nine patterns of cross-reactivity have been defined by CML assays. These results are in agreement with an extend previously described cross-reactivity studies. The reactivities of three monoclonal antibodies previously thought to be reacting with B2M-B are shown to differ: Ly-m11 and J-5 react with cells of strain B10-pa,at and clone 23 does not. Two H-3 region loci are hypothesized on the basis of CML and serologic activity: B2m and H-3. The CTL responses to the B2M antigens are H-2K restricted; the CTL responses to H-3 antigens are H-2D restricted. The restriction of the response to the H-3 antigen requires effector-target identity of the H-2D molecule but not the B2M molecule of the class I antigen. These loci have been separated by recombination from H-42 in the production of the congenic strain B10.FS-a. A gene order of B2m, H-3, H-42 is suggested.

Animals↗
PubMed1985

Immune responses in vitro. XIII. MLR detectability of Mlsa-, Mlsb-, Mlsc-, and Mlsd-encoded products.

The Mls locus was originally defined to have four alleles; all controlled products that were detectable in MLR except b, which was described as being null. More recent evidence led other investigators to postulate that the Mls locus is nonpolymorphic, being composed of only the b null allele and a singly expressed allele previously ascribed to be the a and d alleles. Our results indicate that Mlsa and Mlsd control products that are antigenically distinct and, therefore, the products cannot be controlled by the same allele. In addition, the product of Mlsb was easily detectable by Mlsa and Mlsd responding cells and cannot be considered null. Alternative explanations are considered for these conflicting results.

Animals↗
PubMed1984

Immune responses in vitro, XIV. Undetectability of Mlsb- and Mlsc-encoded products on F1 cells possessing Mlsa or Mlsd.

The Mls locus was originally defined to have four alleles; three controlled products that were detectable in primary mixed leukocyte reactions (MLR), whereas one, b, was described as being null. Recently, other investigators postulated that the Mls locus is nonpolymorphic, being composed of the b null allele and of a singly expressed allele previously thought to be the a and d alleles. We previously reported that products controlled by Mlsa and Mlsd were antigenically distinct and therefore are not controlled by the same allele, and the product of Mlsb on cells of three different strains was easily detectable by Mlsa and Mlsd responding cells. Thus the b allele is not null. In the present report evidence is presented which indicates that both Mlsb and Mlsc encoded products were undetectable by MLR when in the presence of Mlsa or Mlsd. This was demonstrated by the inability of Mlsa/Mlsc and Mlsa/Mlsb F1 cells to stimulate Mlsa responding cells and Mlsd/Mlsc and Mlsd/Mlsb cells to stimulate Mlsd cells; the positive response of Mlsa/Mlsb and Mlsd/Mlsb F1-hybrid cells to Mlsb-encoded products; and the reactivity of Mlsa/Mlsc and Mlsd/Mlsc F1 hybrid cells to Mlsc-encoded determinants.

Alleles↗