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Biomedical subjects

A J Strelkauskas

Publications and source records attributed to A J Strelkauskas.

18 recordsLinked to original sources
PubMed1979

Abnormalities of immunoregulatory T cells in disorders of immune function.

We studied a five-year-old girl with several autoimmune disorders and a 16-year-old boy with acquired agammaglobulinemia to determine whether aberrations of immunoregulatory T cells could explain some instances of immunodeficiency or autoimmunity. The normal peripheral blood T-cell population, as defined by specific heteroantiserums, is 20 per cent TH2+ and 80 per cent TH2-. Human suppressor cells are TH2+, whereas helper cells are TH2-. In addition, each subset expresses Ia antigens upon activation. Our patient with autoimmune disease had no demonstrable TH2+ cells, and her lymphocytes could not be induced to suppress. Her circulating T cells were of an activated-helper phenotype, i.e., TH2-,Ia+. In contrast, in the boy with agammaglobulinemia, the T-cell population was predominantly of an activated-suppressor phenotype, i.e., TH2+,Ia+. This patient's T cells abrogated both his own and his histoidentical brother's B-cell secretion of immunoglobulins. We conclude that the characterization of T cells may provide insight into the causes of a number of abnormal immune states in man.

Adolescent↗
PubMed1979

Phenotypic and functional distinctions between the TH2+ and JRA+ T cell subsets in man.

Prior work has demonstrated the existence of distinct human peripheral blood T cell subsets by utilizing heterologous as well as autoimmune antisera. In the present study, the relationship between the TH2+ and JRA+ T cell subsets was examined. T cells were purified with Sephadex G-200 anti-F(ab)2' affinity chromatography and E-rosetting technique, and subsequently fractionated into TH2+ and TH2- subsets by utilizing indirect immunofluorescence on FACS. Approximately 40 to 45% of the TH2- subset was shown to be JRA+, whereas less than 5% of the TH2+ subset was JRA+. In reciprocal studies, T cells were fractionated into JRA+ and JRA- subsets and reacted with heterologous antisera with anti-TH2+ specificity and indirect immunofluorescence. FACS analysis demonstrated that the JRA+ population contained no TH2+ T cells. In contrast, the JRA- population contained TH2+ T cells and accounted for the entire TH2+ subset found in the unfractionated T cell population. Functional studies showed that the TH2+ subset, and not the JRA+ subset, contain the effector population for cell-mediated lympholysis. It is concluded that the TH2+ and JRA+ T cell subsets define distinct and different T cell populations in man.

Antilymphocyte Serum↗
PubMed1979

Markers of human T cell subsets identified by alloantisera.

Analysis by the indirect fluorescence test followed by fluorescence-activated cell sorter (FACS) analysis has shown that antisera recognizing subsets of human T lymphocytes can be produced by planned immunizations involving HLA-A and HLA-B compatible donors. The reactivity of these antisera against some individuals of a population but not others shows that they recognize a polymorphic cell surface component. The reactive subpopulation largely overlaps with the JRA+ subset, which was previously shown to possess regulatory properties in functional assays. The specificity of the antisera for a T cell subset and the unrelatedness of the anti-B cell activity of the same antisera has been confirmed by two-color fluorescence tests.

Antibody Specificity↗
PubMed1978

Direct evidence for loss of human suppressor cells during active autoimmune disease.

These studies indicate that a regulatory subset of lymphocytes is missing in patients with juvenile rheumatoid arthritis but these patients have antibodies in their serum that react with normal T cells. This regulatory subset of T cells is, however, present in patients whose serum shows little or no reactivity with normal T cells. In addition, patients who are deficient in this regulatory subset of lymphocytes significantly higher numbers of cells secreting Ig as measured by a hemolytic plaque assay. The significance of these observations is twofold: first, they represent a positive relationship among the loss of regulation overproduction of immunoglobulin, and the presence of anti-T cell antibodies and second and perhaps of equal importance, is the indication that serum from patients with autoimmune diseases may give us a readily available reagent with which to dissect further functionally distinct subsets of normal T cells in man.

Adolescent↗
PubMed1978

Isolation and characterization of naturally occurring subclasses of human peripheral blood T cells with regulatory functions.

By utilizing naturally occurring autoimmune antibodies from patients with juvenile rheumatoid arthritis, we have isolated and functionally characterized two unique subpopulations of T cells. JRA+ T cells, i.e., those identified by sera from these patients, react poorly in response to allogeneic cells, respond to Con A but not PHA, and do not help in the synthesis and secretion of Ig by B cells. In contrast, JRA- T cells, i.e., those not identified by sera from these patients, respond very well to allogeneic cells, proliferate well in response to PHA but not Con A, and more interestingly, can greatly enhance the secretion of Ig by B cells.

Antigens↗
PubMed1978

Longitudinal studies showing alterations in the levels and functional response of T and B lymphocytes in human pregnancy.

Altered blood levels of T and B lymphocytes were found in the first half of human pregnancy. A total of twenty-two women were tested, using direct or indirect rosetting assays or the fluorescence-activated cell sorter, to determine the levels of peripheral blood T and B cells. In all cases, an inversion of T- and B-cell levels was observed, i.e. T-cell levels were decreased and B-cell levels (as measured by the presence of surface immunoglobulin or the presence of B-cell surface antigens) were increased. This inversion was exhibited as early as 1 week post-implantation. Lymphocytes from two fo the women were also examined for stimulation with phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) at intervals during gestation, and the amount of [3H]thymidine uptake was compared to that of two non-pregnant women tested at each interval. The values obtained for the pregnant women with PHA were markedly lower, and with pokeweed mitogen slightly lower, than those of non-pregnant controls. However, the PHA and PWM values in the pregnant women returned to levels similar to those of the nonpregnant women shortly after the T- and B-cell levels returned to normal. Thus the decrease in the response of the lymphocytes to mitogens during early pregnancy appears to parallel the numerical deficiency of T cells.

B-Lymphocytes↗
PubMed1977

T-cell regulation of human peripheral blood B-cells responsiveness.

We have investigated the influence of human T cells on the synthesis and secretion of immunoglobulin by peripheral blood B cells. The plaque-forming assay used, which identified the number of B cells secreting Ig, is a short-term assay which requires no exogenous stimulation. We have shown that the B-cell population alone contains fewer secreting cells than the total lymphocyte population, and that T cells are required to achieve maximal plaque-forming cell levels. Cycloheximide treatment of cells at concentrations known to inhibit protein synthesis does not affect the cooperative potential of these cells. Additionally, this cooperation effect is markedly better among autologous mixtures of Ig- and Ig+ cells, than among mixtures obtained from randomly selected individuals.

B-Lymphocytes↗
PubMed1977

Lymphocyte subpopulations in multiple scerlosis: comparison with neuroelectric blocking activity.

Lymphocyte subpopulations were determined in patients with confirmed multiple sclerosis using a new technique in which immunoglobulin bearing (lg+) cells are rosetted directly with purified anti-light chain antibody-coated human erythrocytes, while T cells are first sensitized with specific anti-human thymus antisera prepared in b4b4 rabbits, and then indirectly rosetted with purified anti-rabbit light chain allotype antibody-coated human erythrocytes. In 45 percent of the patients, there was a striking decrease in the percentage of T lymphocytes and a reciprocal elevation of lg+ and N cells. In another 20 percent, T cell depression was not accompanied by Ig+ elevation. The remaining 35 percent had normal lymphocyte profiles as did all patients with nondemyelinating neurologic diseases. However, we found no significant correlation between the lymphocyte profiles and prospective clinical evaluation of these patients and no correlation between alterations in lymphocyte profile and the presence of neuroelectric blocking factors in the peripheral blood of multiple sclerosis patients.

Amyotrophic Lateral Sclerosis↗
PubMed1976

Alteration of lymphocyte subpopulations with cytomegalovirus infection in infancy.

The distribution of immunoglobulin bearing (Ig+), T, and null lymphocyte subpopulations and the lymphocyte response to phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) were determined in three infants with cytomegalovirus (CMV) infection. These infants had significantly decreased percentages of T cells (13%, 29% and 40%) compared to age-matched controls (61 +/- 2%). Compensatory increases in the percentages of Ig+ and null cells occurred. Decreased lymphocyte reactivity to PHA and PWM occurred in two patients. Purified T cells from these patients had normal reactivity indicating a disproportion of T cells in the peripheral blood. These abnormalities may result from CMV infection of lymphocytes and could be responsible for prolonged CMV viruria.

Cytomegalovirus Infections↗
PubMed1975

Enumeration and isolation of human T and B lymphocytes by rosette formation with antibody-coated erythrocytes.

Rosette techniques are presented for the enumeration and separation of both Ig+ T- and Ig- T+ human lymphocytes. In order to enumerate Ig+ cells, the direct immunocytoadhesion technique was employed using human erythrocytes (E) coated with purified anti-kappa or anti-lambda light chain antibodies. Specificity of these rosettes was shown with chronic lymphocytic leukaemias of either the kappa or lambda type. T+ cells were enumerated by a new indirect rosette technique in which the lymphocytes were initially treated with rabbit anti-human thymus cell antiserum followed by direct rosetting with human E coated with purified anti-rabbit light chain antibody. For normal individuals, 24-32% Ig+ T- cells and 65-71% Ig- T+ cells were found among the lymphocytes of peripheral blood as well as tonsils with these rosette methods. The Ficoll-Hypaque method was used to obtain purified Ig- T+ and Ig+ T- cells by removing rosetted Ig+ cells or T+ cells, respectively. The purity of the Ig- T+ cells was indicated by greater than 99% indirect rosetting of cells sensitized with anti-human thymus cell antibody (Ab) and by less than 1% direct rosetting with anti-kappa Ab-E+ anti-lambda Ab-E. The purity of the Ig+ T- cells obtained was indicated by 92-96% direct rosetting with anti-kappa Ab-E+anti-lambda Ab-E and by less than 1% indirect rosetting with anti-human thymus cell antibody. A small percentage of Ig- T- 'null' cells could not be identified by either reagent. Thus, essentially pure Ig- T+ and Ig+ T- cells were readily and efficiently isolated by 'negative selection' thereby lessening the possibility of functional changes that may develop by more extensive manipulation of lymphocytes.

Antibodies↗