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F T Koster

Publications and source records attributed to F T Koster.

At least 37 records · Page 2Linked to original sources
PubMed1989

Effect of conjugate size on the kinetics of cell-mediated cytotoxicity at the population level.

We developed a model for the kinetics of target cell lysis by cytotoxic T-lymphocytes which accounts for most facts observed at the population level. In contrast to previous models, the following facts: conjugate frequency of cytotoxic T-lymphocytes bound to target cell, dependence of this frequency on the lymphocyte-to-target ratio (R), variation of R with time as target cells are destroyed, and population distributions of the different types of conjugates formed between lymphocytes and target cells, which are involved in the kinetics of these kinds of effector-target systems have been contemplated in the model. The relationship with effector-kinetic analogy models for the lytic process has been discussed. Predictions of the model have been explored and compared with experimental observations about target cell lysis reported in the literature.

Cytotoxicity, Immunologic↗
PubMed1989

The maximum conjugate frequency (alpha max) characterizes killer cell populations.

A quantitative procedure to characterize NK cell populations based on the dependence of the frequency of conjugation (alpha) on the effector-to-target ratio (R) is shown. To this end, a detailed study of the influence exerted by: (a) the value of R; (b) the number of effector and target cells (N, T); and (c) the source (donor) and enrichment of the effector cell population on the frequency of conjugation between NK effector and K562 target cells has been performed. This has demonstrated that for a given value of R large differences in the values of alpha can be obtained for different donors and/or N values. Hence, the usual practice of reporting the frequency of conjugation at a given value of R cannot be used as a valid criterion for comparison, and this could explain the differences in the alpha values reported in the literature for the same effector-target system. Moreover, the frequency of conjugation depends on the enrichment of the effector cell populations, although it has been shown that in all cases a plot of 1/alpha vs. R for N = constant is always linear with intercept 1/alpha max.alpha max represents the maximum frequency of conjugation for an effector-target system and remains constant for all values of R and N, and is also independent on the donor of the cell source. These characteristics make that the values of alpha max can be used as an easy criterion to determine with accuracy conjugate frequencies in an effector-target system, and could also be applied to characterize the activation or inhibition of effector cell populations by monoclonal antibodies or other agents. This criterion was applied to characterize the enrichment of NK cell populations and so, a value of alpha max = 58 +/- 3% has been obtained when highly purified (greater than or equal to 99%) NK effector cells obtained by panning with the monoclonal antibodies Leu-2, Leu-3 and Leu-4 are used. However, the corresponding value for MDC (14% NK cells) was lowered to 26 +/- 1%.

Adult↗
PubMed1989

Experimental and theoretical kinetics study of antibacterial killing mediated by human natural killer cells.

We have recently shown that purified human NK cells, both resting and activated, efficiently kill gram-negative and gram-positive bacteria in vitro. To investigate the mechanism of NK cell-mediated cytotoxicity against Escherichia coli we have developed a mathematical model of the kinetics using the experimental data. The kinetics of killing are characterized by initial target bacterial multiplication, followed by rapid bacterial death. Experiments demonstrates that for each donor there is a threshold number of effector cells necessary to observe a net killing effect. Below the threshold, even use of high effector-to-target ratios lack killing activity and the bacterial growth cannot be stopped. In contrast, if the number of NK cells is larger than the threshold, complete killing is achieved, even at ratios as low as 1/1000. The threshold number varies among donors, ranging between 1200 and 12000 purified NK cells/tube, and provides a quantitative measure of antibacterial activity. Performing the assay at 4 degrees C raised the threshold number required for killing. Experiments performed in Boyden chambers confirm that NK cell-bacteria contact is not necessary for efficient killing, although the kinetics of bacterial lysis is slower. The fit between model and data supports the hypothesis that the bactericidal mechanism is extracellular and is mediated by an anti-microbial factor released from NK cells. Accumulated evidence also indicates that this factor is distinguishable from the mechanisms mediating tumor cell cytotoxicity.

Adult↗
PubMed1989

Antibacterial activity of human natural killer cells.

The in vitro effects of human NK cells on viability of Gram-negative and Gram-positive bacteria was investigated. PBLs depleted of glass-adherent cells showed a significant antibacterial activity that was increased as the concentration of NK cells became higher. Leu-11-enriched cells exhibited the most efficient bactericidal activity. Stimulation of NK cells with staphylococcal enterotoxin B for 16 h produced a significant increase in the antibacterial activity of all NK cells tested. The antibacterial activity of monocyte-depleted cells and Leu-11-enriched cells was also enhanced after culturing in vitro for 16-24 h without exogenous cytokines. Dependence of the antibacterial activity on the presence of serum in the culture medium was not found. Ultrastructural studies revealed close contact between NK cell membranes and bacteria, no evidence of phagocytosis, and extracellular bacterial ghosts, after incubation at 37 degrees C. Supernatants from purified NK cells exhibited potent bactericidal activity with kinetics and target specificity similar to that of effector cells. These results document the potent antibacterial activity of purified NK cells and suggest an extracellular mechanism of killing.

Adult↗
PubMed1989

Selective proliferation of natural killer cells among monocyte-depleted peripheral blood mononuclear cells as a result of stimulation with staphylococcal enterotoxin B.

In vitro stimulation of monocyte-depleted peripheral blood mononuclear cells with staphylococcal enterotoxin B (SEB) resulted in selective proliferation of cells which express the phenotypic and functional characteristics of natural killer (NK) cells. This culture system provides an easy method for obtaining highly purified NK cells, by sequential incubation of monocyte-depleted cells with SEB and then with interleukin-2 (IL-2). After culture for 4 to 5 days in the presence of SEB, 98 to 100% of the cells expressed the CD16 (Leu11) and HNK-1 (Leu19) antigens. This purification occurred through the death of lymphocytes lacking NK cell markers and marked proliferation of NK cells themselves, which leads to an enrichment of the NK cell population. Activation of NK cells was detected by the appearance of the gamma interferon receptor and IL-2 receptor antigens. This homogeneous population showed the morphology of large granular lymphocytes, were potent effectors of cell-mediated cytotoxicity against K562 and Daudi tumor cell lines, and were able to kill gram-positive and gram-negative bacteria. IL-2 was necessary to maintain the activation and proliferation after SEB stimulation for 4 days. Moreover, the maximum frequency of binding to K562 cells (60.6%) was similar to that recently found (58 +/- 3%) (P. Garcia-Peñarrubia, F. T. Koster, and A. D. Bankhurst, J. Immunol. Methods 118:199-208, 1989) with fresh and highly purified NK cells. This method can be used as a source of highly purified NK cells to study their functional properties and applications to the treatment of cancer.

Adult↗
PubMed1989

Population distributions of natural killer and K562 target cell conjugates.

We studied the types of conjugates formed at different effector-to-target ratios (R) in the NK-K562 target system. Using purified natural killer (NK) effector cells prepared by a panning technique (greater than 98% CD16), distributions of conjugates are formed such that LTn (one NK cell bound to one or more target cells) are more common at R values less than 1, and LmT (one or more NK cells bound to one target cell) are observed at R greater than 1. Population distributions of these types of conjugates are in agreement with the predictions of the model previously reported for CTL target cell conjugates. In contrast, monocyte-depleted peripheral blood lymphocytes form conjugates in which the LT type is the predominant subpopulation for all values of R. The impact of cell purity on the kinetics and dynamics of cell-mediated cytotoxicity at the population level is discussed.

Adult↗
PubMed1987

Cellular immune competence and diarrheal morbidity in malnourished Bangladeshi children: a prospective field study.

A year-long prospective study of 152 Bangladeshi children with mild to moderate protein-calorie malnutrition related nutritional status and cellular immune defects to morbidity due to diarrheal, respiratory, and febrile diseases. In children older than 36 mo, wasting correlated with skin test anergy to three recall antigens and with inability to initiate hypersensitivity to dinitrochlorobenzene. In this older age group, anergy was associated with a 58% increased attack rate and an 83% increased duration of diarrheal diseases but not with febrile or respiratory infections. In stepwise regression analysis, this anergy effect was independent of the small negative impact of poorer nutritional status on morbidity. Ninety-three percent of diarrheal illnesses lasting at least 14 d were among anergic children. Cellular immune incompetence, indicated by anergy of unknown etiology, is associated with increased diarrheal morbidity and may promote the vicious cycle of repeated infections and deteriorating nutritional status.

Bangladesh↗
PubMed1987

Cellular and humoral immune response to a phenolic glycolipid antigen (PhenGL-I) in patients with leprosy.

The ability of phenolic glycolipid I (PhenGL-I) of Mycobacterium leprae to stimulate in vitro lymphocyte proliferation (LP) was tested in cultures of peripheral blood cells from 42 patients with leprosy in Chicago and Thailand, 9 individuals with household contact in Thailand, and 10 unexposed North American controls. Only 10 responders (24%) were found among the patients, and the degree of LP was small. Responders were found among patients with lepromatous (18%) or tuberculoid (30%) leprosy without relation to age, complications, duration of treatment, or lepromin responsiveness. The specificity of the response was supported by a lack of response to two other glycolipids, by responses by T cells but not B cells, and by the observation that three of four responders tested maintained their responses to PhenGL-I for at least 1 year. Serum immunoglobulin M (IgM) and IgG antibodies were measured in the same patients by using PhenGL-I or its terminal monosaccharide conjugated to a bovine serum albumin carrier in an enzyme-linked immunosorbent assay. The presence of IgM antibody correlated negatively with LP to lepromin and to PhenGL-I in patients with tuberculoid leprosy. We conclude that circulating T cells from some leprosy patients proliferate in the presence of PhenGL-I in vitro, but the response is weak, possibly due to concomitant suppression or inhibition. The predominance of IgM antibody to PhenGL-I may be related to a lack of a T-helper-cell-mediated switch to IgG antibody response.

Antibodies, Bacterial↗
PubMed1986

Strain variations in the murine cellular immune response to the phenolic glycolipid I antigen of Mycobacterium leprae.

The cellular immune response to the Mycobacterium leprae-specific phenolic glycolipid I was examined in inbred mice immunized with M. leprae by in vivo delayed cutaneous hypersensitivity and in vitro lymphocyte proliferation. Whereas all mouse strains responded to M.leprae-induced delayed-type hypersensitivity and lymphocyte proliferation, only BALB.K was responsive in both assays to the glycolipid. Responsiveness was determined in part by non-H-2 genes, while the influence of H-2 genes was not apparent. Among congenic BALB/c mice differing only at Igh-C allotype loci, variations in responsiveness were found in both delayed-type hypersensitivity and lymphocytes proliferation assays, indicating a possible role for Igh-C loci-linked genes. Unresponsiveness in the lymphocyte proliferation assay to the glycolipid was inherited as a dominant trait in one set of responder X nonresponder F1 progeny. We conclude that after immunization with M. leprae organisms, the cell-mediated responses to the glycolipid, endowed with a single carbohydrate epitope, are under polygenic control, predominantly non-H-2-linked genes.

Animals↗
PubMed1986

Disseminated macronodular cutaneous candidiasis in chronic alcoholism.

Disseminated candidiasis usually occurs in profoundly immunocompromised hosts. We described a case of disseminated macronodular cutaneous candidiasis in a man with no known risk for immunosuppression other than alcoholic liver disease and a second case of multiple macronodular cutaneous abscesses in an alcoholic man who had no evidence of systemic dissemination. One patient had testicular candidiasis, a previously unreported site of infection in disseminated candidiasis. Tests showed neutrophil and lymphocyte function to be normal; however, a marked defect in serum opsonization was demonstrated in one patient. It is postulated that chronic alcoholism with alcoholic liver disease resulted in impaired serum opsonization, which, in turn, predisposed these patients to candidal infection.

Alcoholism↗
PubMed1985

Cellular immunity in Q fever: specific lymphocyte unresponsiveness in Q fever endocarditis.

Human infection with the rickettsia Coxiella burnetii presents as acute influenza-like primary Q fever, subacute granulomatous hepatitis, or chronic endocarditis with hepatitis. To investigate whether persistent infection is associated with a possible immunologic defect, we tested lymphocyte proliferation specific for Coxiella in vitro in peripheral blood mononuclear cells from patients and controls. All four patients with endocarditis had profound lymphocyte unresponsiveness to Coxiella antigens with normal proliferation to control antigens. Hepatitis and primary Q fever were associated with vigorous responses in vitro to Coxiella antigens. Suppression of lymphocyte unresponsiveness was in part mediated by an antigen-nonspecific, glass-adherent cell. We hypothesize that specific T cell unresponsiveness is an important factor in persistent infection with C. burnetii and offer in vitro lymphocyte stimulation as a more specific diagnostic test to distinguish cases of endocarditis among those with chronic hepatitis due to Q fever.

Adult↗
PubMed1985

Antibody response to phenolic glycolipid I in inbred mice immunized with Mycobacterium leprae.

The level of circulating antibody to phenolic glycolipid I of Mycobacterium leprae was determined in 18 inbred strains of mice after immunization with M. leprae organisms. By using a solid-phase radioimmunoassay with phenolic glycolipid I as test antigen, a continuous distribution of antibody levels ranging from high to low was observed. The level was found to be controlled by multiple genes, including both H-2 complex- and Igh allotype complex-linked genes. Low antibody response to phenolic glycolipid I was shown to be inherited as a dominant trait in three combinations of high X low responder F1 progeny.

Animals↗
PubMed1985

Cellular immunity in Q fever: modulation of responsiveness by a suppressor T cell-monocyte circuit.

Human infection with the rickettsia Coxiella burnetii presents as an acute flulike primary Q fever, as a subacute granulomatous hepatitis, or, rarely, as chronic endocarditis. We have previously described lymphocyte unresponsiveness to Coxiella antigen in patients with Q fever endocarditis. This unresponsiveness was antigen specific and was mediated in part by adherent suppressor cells. In this report we show that the adherent suppressor cells work via prostaglandin E2 (PGE2)4 production. Addition of the cyclooxygenase inhibitor indomethacin to cultures of PBMC from patients with endocarditis or chronic laboratory exposure resulted in consistent increases in Coxiella-specific lymphocyte proliferation. The degree of increase in proliferation induced by indomethacin correlated strongly with the amount of PGE2 produced in a 4-hr culture stimulated by Coxiella antigen, but it also correlated with the sensitivity to inhibition of mitogenesis by PGE2. The suppressor mechanism was antigen nonspecific, because induction of suppression in vitro by Coxiella antigen also suppressed Candida-induced proliferation when both antigens were present in the same culture. Addition of indomethacin to these antigen cocultures totally reversed the Coxiella-induced suppression, confirming the evidence above that the nonspecific effector mechanism of suppression was prostaglandin (PG)-mediated. Elicitation of suppression, however, was antigen specific and involved a T cell-monocyte suppressor circuit. Supernatants from Coxiella-stimulated immune T cells and from the suppressor subset (OKT8+-enriched) of those T cells, but not unstimulated immune cells, induced augmented PGE2 production by unrelated nonimmune PBMC. We conclude that the lymphocyte unresponsiveness characterizing patients with Q fever endocarditis is modulated in part by an antigen-specific T suppressor cell which secretes a lymphokine to stimulate PGE2 production by adherent cells.

Adult↗
PubMed1984

Antibody-dependent cellular cytotoxicity of Coxiella burnetii-infected J774 macrophage target cells.

Cell-mediated immunity is clearly the critical host defense mechanism against human Coxiella burnetii infection (Q fever); the role of specific antibody is unclear. By using a mouse macrophage tumor cell line, J774, persistently infected with C. burnetii phase I organisms, in a standard 51Cr-release cytotoxicity assay, we explored the possibility that antibody-dependent cellular cytotoxicity may be immune mechanism in Q fever. After 16 h of incubation in the presence of immune sera from Q fever hepatitis or endocarditis patients, nonimmune human peripheral blood effector cells specifically lysed infected J774 target cells; no 51Cr release was seen in the presence of nonimmune sera or uninfected target cells. An effector/target ratio of at least 5:1 was required, and monocytes were more efficient effector cells than lymphocytes. Cytotoxicity was blocked by preincubation of effector cells with purified aggregated human immunoglobulin G, indicating the role of Fc receptor-bearing effector cells. Two nonphagocytic lymphoid tumor cell targets, passively coated with C. burnetii, did not induce substantial immune-specific cytolysis, suggesting that bystander lysis does not explain the observation of specific lysis. Although antibody-dependent cellular cytotoxicity may participate in primary defense, alternatively, it may facilitate the dissemination of C. burnetii or surreptitiously participate in granuloma formation.

Animals↗
PubMed1984

Renal histopathology in the hemolytic-uremic syndrome following shigellosis.

The hemolytic-uremic syndrome (HUS) following dysentery caused by S. dysenteriae Type 1, characterized by microangiopathic hemolytic anemia and acute renal insufficiency, is clinically similar but not identical to the idiopathic HUS. We studied renal necropsy specimens of nine children who died of HUS following shigellosis by light and immunofluorescent microscopy and compared them to 12 controls: six cases with severe shigellosis without HUS, and six with pneumonia or sepsis. Eight of nine HUS cases showed cortical necrosis, extensive glomerular thrombosis or arterial thrombosis. Cases without HUS showed only scattered glomerular fibrin thrombin and widening of the mesangium. Among seven HUS cases studied by immunofluorescent microscopy, three demonstrated deposition of glomerular IgM and complement (C3) and one of the three had IgG and IgA as well; four cases had neither immunoglobulin or complement deposits. Among nine controls, two demonstrated IgM and three IgG, but none had C3. Both HUS and non-HUS cases had fibrin deposition. In the three HUS cases studied by electron microscopy intracapillary material (fibrin and platelets) was seen in all three, and sparse electron-dense deposits in mesangial matrix in one. The data indicate that the renal histopathology in the HUS following shigellosis consistently presents as a severe thrombotic microangiopathy, but lacks the characteristic endothelial and mesangial lesions of idiopathic HUS. The infrequent demonstration of glomerular immunoglobulin deposition fails to support an immunoglobulin-mediated pathogenesis.

Anemia, Hemolytic↗
PubMed1983

Alterations in lymphocyte cell surface markers during various human infections.

Peripheral blood lymphocyte cell surface markers were studied in 146 patients with various forms of acute infection using B cell identification with antisurface immunoglobulin and T cell subset enumeration with hybridoma T cell subpopulation reagents. Significant depression was recorded in total numbers of T cells and T cell helper-inducer and suppressor-cytotoxic subsets in pneumonia, acute pyelonephritis, and severe generalized sepsis. In addition, proportions of T cells being the OKT4 helper-inducer phenotype were reduced only in patients over the age of 60 with pneumonia or sepsis. Patients with severe infection frequently had multiple T cell phenotypic surface marker abnormalities. In some instances, when depressions of total T cell numbers as well as respective helper-inducer or suppressor-cytotoxic T cells were noted in the face of generalized sepsis, lack of improvement in these abnormalities during the course of treatment was associated with rapid clinical deterioration and death. On the contrary, in patients with a successful response to appropriate therapy, initial depressions of total T cell numbers and subsets improved progressively with clinical resolution of sepsis and illness.

Adult↗
PubMed1983

Parenteral immunization causes antigen-specific cell-mediated suppression of an intestinal IgA response.

Rats immunized s.c. with cholera toxin (CT) or toxoid (CTd) show antigen-specific suppression of the jejunal IgA anti-CT response to subsequent enteric doses of CT. We determined whether this effect was partly cell-mediated and studied the suppressor cell response involved. Spleen cells from s.c.-immunized rats suppressed the jejunal anti-CT response in adoptive recipients when cell transfer was at, or 4 days before, intraduodenal priming with CT. Transferred suppression was antigen-specific, and the suppressor cells were nylon wool-nonadherent. Increasing the s.c. dose of CT from 0.1 to 40 micrograms, and the interval between immunization and cell harvest from 2 to 16 wk, each increased the suppressive effect of a constant spleen cell inoculum. After s.c. immunization, suppressor cells were present in the spleen within 1 to 2 wk, among TDL within 4 to 8 wk, and in Peyer's patches and thymus within 8 to 16 wk; this sequence suggested they arose in the spleen and later migrated to mucosae and the thymus. Prior splenectomy did not alter the suppressive effect of s.c. CT, however, nor did it prevent suppressor cell appearance among TDL, indicating that suppressor cells also arose from nonsplenic sites. Transferred suppressor cells acted by interfering with the development of specific immunologic memory within Peyer's patches during enteric priming; transfer of suppressor cells at the time of enteric boosting had no effect upon the secondary mucosal anti-CT response. We conclude that the suppressive effect of s.c. immunization on a specific mucosal IgA response is due largely to the action of systemically derived suppressor cells upon the primary mucosal immune response within Peyer's patches. This sequence resembles the mirror image of oral tolerance, which involves the suppression of systemic IgG and IgM responses by suppressor cells that arise in Peyer's patches and migrate to the spleen after antigen feeding.

Animals↗