T-cell Rosette Formation Research Articles

Interaction of Plasmodium falciparum histidine-rich protein II with human lymphocytes leads to suppression of proliferation, IFN-γ release, and CD69 expression

The presence of histidine-rich protein II (HRP II) synthesized by Plasmodium falciparum in the plasma of malaria patients for longer periods even after parasite clearance raises questions about its extracellular functions. The present study was carried out to examine its influence on host immune system. Recombinant HRP-II protein was radiolabeled with (125)I to study the specific binding with T and B cells. We found that the binding of (125)I-HRP II with human T and B cells was specific, concentration dependent, saturable, and reversible. Scatchard plot analysis revealed two classes of binding sites for both T and B cells. For the T cells, the high affinity class had dissociation constant (K(d)) of 5.61x10(-11)M, and the low affinity class had a K(d) of 8.58x10(-11) M. For the B cells, the high and low affinity classes had a K(d) of 1.32x10(-11) and 2.84x10(-11) M, respectively. Dot-blot, autoradiography, and Western blot analysis also confirmed the specific binding of HRP II with lymphocytes. HRP II significantly inhibited (approximately 75%) T-cell rosette formation with sheep erythrocytes. HRP II also suppressed proliferation of T and B cells triggered by CD3 and LPS, respectively. We found a reduction in IFN-gamma release in T cells preincubated with HRP II. HRP II also reduced the CD69 expression on the T cells. In conclusion, HRP-II binding to human lymphocytes leads to suppression of some of their functions.

A multimeric form of soluble recombinant sheep LFA-3 (CD58) inhibits human T-cell proliferation.

The rosetting of T cells by sheep erythrocytes is mediated through the interaction of the CD2 molecule on T cells with T11TS, a molecule on sheep erythrocytes homologous to lymphocyte function-associated antigen-3 (LFA-3, CD58). We cloned a T11TS cDNA from sheep leucocyte mRNA which encodes a soluble molecule comprising the distal D1 and the D2 extracellular domains, but not the transmembrane domain. cDNA for this soluble D1 + D2 form of sheep LFA-3 (sLFA-3) was expressed in Escherichia coli and the properties of the purified recombinant protein were assessed by inhibition of T-cell rosette formation. sLFA-3 inhibited rosette formation, but its activity was low, 50% inhibition occurring at 25 micrograms/ml, consistent with the observed low binding avidity of fluorescein isothiocyanate (FITC)-labelled sLFA-3, sLFA-3 was made multimeric to increase its affinity, by crosslinking biotinylated sLFA-3 to streptavidin-biotinylated dextran complexes. The binding of crosslinked sLFA-3 multimers, tested by fluorescence-activated cell sorting (FACS) analysis, was significantly increased compared to sLFA-3 monomers. Competition with monoclonal antibodies demonstrated that multimeric sLFA-3 bound to the T11(1) epitope on CD2. The multimeric form of sLFA-3 was significantly more potent than the monomer in inhibiting proliferation of human T cells in response to purified protein derivative (PPD), tetanus toxoid (TT) or allogeneic cells. Multimeric sLFA-3 might, therefore, have potential as an immunotherapeutic agent to inhibit and/or anergize antigen-specific T-cell responses.

Marijuana and host resistance to herpesvirus infection.

The marijuana plant contains in excess of 400 chemical entities, of which 60 or more are cannabinoids (1). Delta-9-tetrahydrocannabinol (THC) is the major psychoactive cannabinoid in marijuana and has been shown to induce immunosuppressive effects both in vivo and in vitro. The drug inhibits lymphocyte responsiveness to mitogens and particulate antigens (2), decreases T-cell rosette formation (3,4), suppresses leukocyte migration (5), and alters macrophage morphology, function, motility, and protein expression (6–8).KeywordsSpleen MassMurine L929 CellInfected L929 CellCell Surface BlebCytoplasmic PolarizationThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

The effect of thymopoietin II fragments and their analogs on E-rosette forming cells in the uremic state.

The synthesis of four fragments from dipeptide to pentapeptide, corresponding to amino acids 32 to 36 of thymopoietin II, and four analogs is described, together with their effects on E-rosette forming cells in the uremic state. After incubation with amounts of H-Arg-Lys-Asp-Val-Tyr-OH (residues 32-36) varying from 100 to 200 μg/ml of cell suspension, maximum T-cell rosette formation ranged from 65 to 73% compared with 50 to 52% without the peptide. The activity of H-Arg-Lys-Glu-Val-Tyr-OH was lower than that of H-Arg-Lys-Asp-Val-Tyr-OH. The other fragments and analogs had no effect on the E-rosette formation-inhibiting activity of uremic serum at a dose of 200 μg/ml

An Immunosuppressive Serum Factor in Widespread Cutaneous Dermatophytosis

A patient had a widespread dermatophytosis and a serum factor that specifically suppressed his T-cell rosette formation and the phytohemagglutinin responsiveness of his lymphocytes. The patient was also unable to mount a delayed hypersensitivity reaction to a standard anergy panel, although he did exhibit an immediate type hypersensitivity reaction to the trichophytin skin test antigen. Although many immunosuppressed patients succumb to severe bacterial and fungal infections, it is our contention that in certain cases the infectious process itself may generate a serum factor that is capable of inducing immunosuppression, thereby rendering the patient susceptible to further spread of the infection.

Enhanced T-cell rosette formation in shigellosis by the in vitro use of thymopoietin

The results from this study suggest that the large nul cell lymphocyte population seen in patients with Shigella dysentery, does contain a sub-population of cells that will respond in vitro to thymopoietin, a bovine thymic extract, by increased E-rosette formation. It is felt that this sub-population is in fact immature T-cells. A previous study has shown that an unusual leukaemoid reaction develops in a substantial number of patients with Shigella dysentery. The leukaemoid response was primarily granulocytic in nature but there was also a substantial increase in the mean number of lymphocytes. The proportion of the various populations of lymphocytes from leukaemoid and non-leukaemoid subjects were altered, B-cells remained constant, while the T-cells were depressed with a corresponding rise in the proportion of nul cells. The cumulative results of this and other studies demonstrate that the T-cell arm of immunity is compromised in shigellosis. Indeed the degree of compromise may ultimately be the decisive factor in determining the severity of this disease. A previous study ( Jackson et al., 1979) of the sub-populations of peripheral blood lymphocytes from patients with Shigella dysentery indicated an imbalance in the proportion of T, B, and nul cell lymphocytes. The proportion of B-cells remained constant, while the T-cells were depressed with a corresponding rise in the proportion of nul cells. It was suggested that some of these nul cells were in fact immature T-cells. To support this hypothesis peripheral blood lymphocytes from Shigella patients were incubated with a bovine thymic extract, thymopoietin, to determine if such an exposure would increase the percentage of T-cells.

Inhibition of human T-cell rosette formation by the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (EHNA)

Mononuclear cell surface markers from normal human volunteers were tested in the presence of the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (EHNA). Only the T-cell surface marker, formation of rosettes with sheep red blood cells, was significantly inhibited by concentrations of EHNA in a dose-dependent manner. Metabolic compartmentalization of adenosine compounds at the site of nucleoside transport across the cell membrane may play an important role in determining T-cell rosette formation and whether or not the blastogenic response of these cells to environmental mitogens will occur.

Inhibition of T-Cell Rosette Formation by Hodgkin-Disease Serum

After more than a decade of investigation of lymphoid subpopulations through the use of cell markers, some recent studies are beginning to provide insights into the mysterious process known as Hodgkin's disease. Several different groups working in the field have found conflicting results, reporting either normal or reduced proportions of thymus-dependent (T) cells, usually determined by the ability of these lymphocytes to form rosettes with sheep erythrocytes.1 In 1974, Bobrove, Fuks, Strober and Kaplan reported that although the proportion of T cells in their patients was normal when measured with a specific anti-T-cell antiserum, many such cells failed to form . . .

Fractionation of normal human bone marrow on albumin gradients

Bone marrow from 52 healthy donors has been fractionated on two discontinuous albumin gradients with different osmolarities in an effort to eliminate immunocompetent cells and to isolate hemopoietic stem cells. The nutrient agar system of Robinson was utilised as an assay procedure for the detection of colony-forming cells (CFU-c) in the resulting fractions. CFU-c, early granulocytic progenitors, are consistently present in the lighter fractions. On cytochemical staining, they showed a positive reaction for enzymes bound to lysosomes. The concentration of CFU-c was in an average 7 times that of the original marrow. At best, 1 X 10(5) CFU-c could be isolated from 10 ml marrow corresponding to 2 X 10(8) buffy-coat cells. The presence of immunocompetent cells was monitored by Phytohemagglutinin (PHA)-stimulation and T-cell rosette formation. In a human marrow transplant situation it appears that a better yield of CFU-c is necessary than is afforded by albumin gradient technique.

Marihuana, tetrahydrocannabinol and T-cell function

Conflicting reports exhist on the effect of marihuana smoking on thymus derived lymphocytes (T-cells). Marihuana smoking has been reported to both reduce the formation of T-rosettes and affect mitogenic stimulation of T-cells in man. This present study was conducted to evaluate the effects of marihuana smoking on T-cells during a 24-hour period after smoking. Chronic marihuana smokers, who had abstained from smoking for one month, smoked “street” marihuana, marihuana cigarettes with a known quantity of delta-9-tetrahydrocannabinol (THC), or placebo marihuana cigarettes. In two of three subjects who used “street” marihuana, T-cell rosette formation was reduced 24 hours after smoking. Response to phytohemagglutinin (PHA) stimulation was reduced in one of the above subjects. In a second group of subjects, rosette formation was decreased in five of six subjects 3 to 6 hours after smoking marihuana cigarettes containing 10 mg of THC. However, values in all but one individual returned to control levels within 24 hours. A 50% reduction in PHA stimulation was also observed in this subject 6 hours after smoking. PHA stimulation was not affected following placebo. In the sixth subject, a stimulatory effect on rosette formation was observed following both the use of the THC-containing and placebo marihuana cigarettes. The results of these studies indicate that while marihuana smoking affects certain in vitro tests of T-cell function, the effects are variable, transitory, and may be associated with factors other than THC.

Elevated IGA in carcinoma of the nasopharynx.

Fourteen patients with nasopharyngeal carcinoma were evaluated immunologically prior to standard radiotion therapy. All had elevations of serum IgA, ranging from 300 mg/100 ml to 1000 mg/100 ml, with a mean value of 549 mg/100 ml. Seven patients demonstrated depression of cell-mediated immunity as measured by delayed hypersensitivity skin tests, total lymphocyte count, in vitro stimulation with PHA, and T-cell rosette formation. Elevation of serum IgA associated with depression of cell mediated immunity may be characteristic of patients with nasopharyngeal carcinoma.

NUCLEOSIDE-PHOSPHORYLASE DEFICIENCY IN A CHILD WITH SEVERELY DEFECTIVE T-CELL IMMUNITY AND NORMAL B-CELL IMMUNITY

A 5-year-old girl with a history of recurrent infection and anæmia has no measurable purine nucleoside phosphorylase (N.P.) activity in her red blood-cells. Her serum-immunoglobulin levels are normal, as are her antibody responses to thymus dependent and independent antigens. However, she has severe lymphopenia, pronounced depression of lymphocyte response to mitogenic and allogeneic cell stimuli, and greatly decreased T-cell rosette formation. Her parents are second cousins, their red cells contain less than half the normal level of N.P. activity. They also share an unusual N.P. isozyme pattern indicative of molecular hybridisation between catalytically active and inactive subunits, which strongly supports the assumption that they are heterozygous and their daughter is homozygous for a "silent" allele at the N.P. gene locus. Inherited deficiency of adenosine deaminase, an enzyme catalysing a reaction only one metabolic step away from that of N.P., is known to cause immunodeficiency. It is therefore very likely that this patient's lack of demonstrable N.P. activity is responsible for her syndrome.

RECONSTITUTION OF CELLULAR IMMUNITY IN PATIENTS WITH SEVERE COMBINED IMMUNODEFICIENCY BY FETAL THYMUS TRANSPLANTATION AND TRANSFER FACTOR

Reconstitution of cellular immunity in 3 infants occurred following intraperitoneal fetal thymus transplantation and Transfer Factor therapy. In all 3, the earliest evidence of reconstitution was a rash consistent with graft vs host reaction (GVHR) with onset 10 to 14 days following transplant. Mild GVHR occurred in the 1- and 4-mo old infants who were apparently free of infection at the time of thymus transplantation from 12- and 14-week fetuses. These 2 infants are alive and well at age 2-½ yr and 11 mos. Severe GVHR occurred in the S-mo old infant following thymus transplant from a 16-week fetus; the infant was receiving therapy for pneumocystis carinii at the time of transplant. The child died 10 wks post-transplant with GVHR and pulmonary disease. The sequence of cellular reconstitution in all infants was lymphocyte response to allogenic cells, phytohemagglutinin, and T-cell rosette formation and occurred 3 to 12 wks following transplantation. Cell chimerism was detected by HL-A typing in 2 infants. Reconstitution of antibody-mediated immunity was not observed. Successful reconstitution in these patients, in contrast to earlier experience, was probably related to 3 factors: synergism between thymus and Transfer Factor, transplant of thymus within 1 hr after fetal abortion, and transplantation prior to severe infection.

FAMILIAL IMMUNE DEFICIENCY AND LEUKODYSTROPHY: RECONSTITUTION WITH FETAL THYMUS IN A MILLIPORE CHAMBER

A 2 ½ year old male child (D.E.) with multiple congenital anomalies, severe psychomotor retardation, generalized seizures, chronic herpetie gingivostomatitis, overwhelming pneumococcal meningitis and sepsis was found to have a partial combined immunodeficiency. His female sibling (J. E.) who followed a similar course and who died at 4 ½ years of age was found to have sudanophilic leukodystrophy. During the course of his hospitalization, D. E. developed intractable diarrhea and was noted to have a decreased lymphoproliferative response to PHA, decreased T-cell rosette formation, a persistent lymphopenia and normal erythrocyte adenine deaminase (ADA) activity. Immunoglobulin therapy and parenteral hyperalimentation failed to alter his clinical course. Following transplantation of a 16-week fetal thymus enclosed in a millipore chamber there was prompt clearing of the herpetie lesions and cessation of the diarrhea within a few days after transplantation and an appearance of lymphocyte responsiveness to PHA one month later. Nine months after transplantation the patient remains infection-free and continues to display an intact cellular immunity. This report describes a previously unrecognized presentation of combined immune deficiency and suggests a new approach to therapy.