Opposing effects of human peripheral blood lymphocytes on the growth of cultured leukemia cell lines.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
J F Carlquist
Publications and source records attributed to J F Carlquist.
Progressive resistance in a single strain of Acinetobacter calcoaceticus recovered during a nosocomial outbreak.
A study was undertaken to investigate a nosocomial outbreak of acinetobacter calcoaceticus. The outbreak occurred in a shock-trauma intensive care unit (ICU) during a 6-month period and involved a total of 37 cases. Although no deaths were attributable to Acinetobacter, 60% of patients from whom Acinetobacter was isolated were determined to have a lower respiratory tract infection. A significant difference (p less than 0.05) was noted between the length to stay in the unit of patients who acquired Acinetobacter (mean 23.9 days) and of those who remained free of the organism (mean 2.58 days). The average day on which cultures first became positive was 14.85. During the last 3 months of the outbreak, the ICU Acinetobacter isolates developed an unusual pattern of aminoglycoside resistance that differed significantly (p less than 0.001) from the sensitivities of non-ICU Acinetobacter isolates. No plasmids could be detected in selected aminoglycoside-resistance Acinetobacter. Pseudomonas aeruginosa isolated concurrently from patients with Acinetobacter showed no abnormal variation in antimicrobial sensitivities. These findings were interpreted to mean that the outbreak was the result of the persistence of a single strain of A. calcoaceticus within the ICU. Termination of the outbreak was attributed to initiation of control measures.
Acinetobacter↗
Mitogenic factor from chronically infected guinea pigs.
A lymphokine produced by antigen stimulated lymphocytes, induces blastogenesis in cultures of lymphocytes which are not sensitive to the specific antigen. The in vitro production of this factor (MF) was accomplished utilizing peritoneal exudate (PE) cells from Coccidioides immitis infected guinea pigs. Production of MF by lymphoid cultures paralleled skin test reactivity of the donor animal. Removal of adherent cells from the PE population did not decrease the production of MF; conversely, a more significant production of MF was effected by the adherent cell depleted populations. Maximal production of MF was achieved at non-adherent cell concentrations from 4 X 10(6) to 8 X 10(6) cells/ml. Cell concentrations below 4 X 10(6)/ml produced material which inhibited DNA synthesis in test cultures. MF was separated from the inhibitory substance(s) by column chromatography of the crude preparations on Sephadex G-75. Inhibitor(s) eluted in the void volume (VO), and the MF eluted in an effluent volume (Ve) which was greater than the total bed volume (Vt) suggesting that MF is adsorbed by Sephadex beads.
Animals↗
Propagation and characterization of lymphocytes from rejecting human cardiac allografts.
In recent years heart transplantation has become an increasingly common therapeutic measure for cases of heart failure not amenable to other forms of management. Despite major advances, graft rejection continues to be the main cause of transplant failure. To expand our knowledge of the rejection process, we have grown lymphocytes from biopsy specimens obtained from potentially rejecting allografts. The growth of the lymphocytes requires the presence of interleukin-2 and was shown to correlate well with histologic criteria in identifying rejection (p less than 0.003, chi-square analysis). Of 125 biopsy specimens, 61 (49%) became positive for lymphocyte growth within 30 days. Of the biopsy specimens that were positive on culture, 54 (88%) were histologically diagnosed as rejecting, and seven (11%) were histologically nonrejecting. Of the 64 specimens that were negative on culture, 28 (44%) were histologically negative for rejection, and 36 (56%) were positive for some grades of rejection. Of these culture negative, microscopically positive specimens, however, 31 (86%) were associated with mild (grade 3) or equivocal (grade 2) rejection. Discrepancies between culture and histology appeared to be related to degree of rejection, quantity of sample, and sampling variation. Phenotypic identification of cultured cells showed that the suppressor/cytotoxic phenotype was the predominant cell type in all cultures (mean +/- standard error = 83% +/- 3% of cells). Antihuman mature inducer/helper T cell (OKT4+) T-lymphocytes in culture were associated with biopsy specimens obtained immediately before onset or at the beginning of rejection. Preliminary studies testing in vitro sensitivities of lymphocytes to antithymocyte globulin (ATG) and other control immunosuppressants not believed to function by direct cytolysis (methylprednisolone, cyclosporine, azathioprine) were undertaken. These yielded reproducible dose-response curves, and the drug concentration producing 50% cytotoxicity (LD50) was calculated for each drug-culture combination. The mean LD50 for ATG was in the range of in vivo therapeutic concentrations, whereas LD50 values for control drugs were threefold to twelvefold higher than therapeutic concentrations. Resistance to the effects of ATG showed a tendency to correlate with prolongation of rejection; however, a similar tendency was noted for control drugs, suggesting the possibility of a nonspecific mechanism of resistance to the effects of ATG. The technique of interleukin-2 lymphocyte culture from rejecting allografts promises to further our understanding of mechanisms of graft rejection.
Adult↗
Phenotype and serine esterase production of human cardiac allograft-infiltrating lymphocytes.
Human cardiac allograft-infiltrating lymphocytes were studied by in vitro expansion in interleukin-2. Of 28 graft-infiltrating lymphocyte cultures from 17 recipients, 17 were comprised predominantly of CD4+ T cells and 10 predominantly CD8+ T cells; one culture had equal numbers of CD4+ and CD8+ cells. The mean percentages (+/- SE) of T-cell subsets for all cultures were as follows: CD4+, 49% +/- 29%; CD8+, 42% +/- 31%. No correlation was observed between the culture phenotype and histologic findings, length of time from transplantation, or number (or class) of mismatched HLA antigens. N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester serine esterase (BLT-SE) is an enzyme associated with intracellular cytotoxic T-cell granules and with target-cell destruction. Sixteen cultures were tested for BLT-SE activity and had significantly increased enzyme activity as compared to untreated peripheral blood mononuclear cells from healthy control subjects (p < 0.002), or interleukin-2-treated control cells (p < 0.05). A low percentage (0.4% +/- 0.2%) of cells in the graft-infiltrating lymphocyte cultures expressed the phenotypic marker NKH-1, suggesting that the source of BLT-SE in these cultures was not natural killer or lymphokine-activated T cells. Elevated BLT-SE was observed in five of ten cultures containing predominantly CD4+ cells and five of six cultures containing predominantly CD8+ T cells. Mixed phenotype graft-infiltrating lymphocyte cultures depleted of either CD4+ or CD8+ T cells retained BLT-SE activity. Thus both CD4+ and CD8+ graft-derived T cells can produce this enzyme although much greater variability in enzyme production was seen for CD4+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)
CD4-Positive T-Lymphocytes↗