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J R Klein

Publications and source records attributed to J R Klein.

At least 109 records · Page 6Linked to original sources

Delayed-type hypersensitivity response in mice to Treponema pallidum.

C3H/HeJ mice which had been primed with either virulent or killed T. pallidum were studied for in vivo delayed-type hypersensitivity (DTH) responses to T. pallidum following local footpad challenge. Mice sustaining a chronic infection of 5 months duration failed to develop a DTH to treponemal antigens, whereas priming by a single intravenous injection with killed organisms resulted in a significant DTH response in mice when challenged 5 days later. Treatment of mice prior to priming with a single sublethal dose of cyclophosphamide (100 mg/kg body weight) not only failed to potentiate T. pallidum-DTH, but abrogated the response observed in untreated primed animals.

Adjuvants, Immunologic↗

Coordinate production by a T cell hybridoma of gamma interferon and three other lymphokine activities: multiple activities of a single lymphokine?

The T cell hybridoma FS7-20, produced by the fusion of normal B10.BR T cells to the AKR thymoma BW5147, was found when stimulated with concanavalin A (Con A) to produce the lymphokines: interleukin 2 (IL 2), interferon-gamma (IFN gamma), macrophage-activating factor (MAF), Ia induction factor IaIF), and the B cell helper factor interleukin X (IL X). The clones and subclones of FS7-20 varied dramatically in their ability to produce these lymphokines, presumably because of karyotypic variations. The ability to produce IL 2 segregated independently from the ability to produce the four other lymphokine activities; however, production of the latter activities showed a strong correlation. This coordinate production of IFN gamma, MAF, IaIF, and IL X was also observed with a cloned normal cytotoxic T cell line, cr15. These results suggest either that IFN gamma, MAF, IaIF, and IL X are all manifestations of a single molecular species or that, although these activities are different structurally, their production is controlled by a common genetic mechanism. In support of the first possibility, the IFN gamma, MAF, IaIF, and IL X activity produced by FS7-20 were all found to be equally sensitive to inactivation at pH 2. These results illustrate the usefulness of using T cell hybridomas for the study of lymphokines.

Animals↗

Secretion of immune interferon and generation of cytotoxic T cell activity in nude mice are dependent on interleukin 2: age-associated endogenous production of interleukin 2 in nude mice.

We have examined the relationship between the Con A-mediated induction of CTL effector function and immune IFN secretion in congenitally athymic nude mice. Spleen cells from young adult nude mice (2 mo of age) were found to require an exogenous source of IL 2 for the activation of a CTL effector response and for the release of immune IFN. However, the response of spleen cells from nude mice 9 mo of age differed from that of younger animals in that exogenous IL 2 was not required for the activation of CTL effector function and immune IFN secretion. Spleen cells from old nude mice were found to be capable of making IL 2 upon Con A stimulation similar to normal thymus-bearing animals. The data demonstrate that the maturation of IL 2-secreting cells can occur in athymic mice, that IL 2 is a requisite signal not only for the development of CTL effector function but also for the production of immune IFN, and that CTL effector function and immune IFN release are closely associated immunologic events.

Aging↗

Epidemiology of adolescent dysmenorrhea.

Dysmenorrhea is the leading cause of recurrent short-term school absenteeism among adolescent girls. Controversy surrounds the relative role of psychologic and biologic variables in the pathogenesis of dysmenorrhea. Therefore, data from 2,699 menarcheal adolescents, drawn from a national probability sample of 12 to 17-year-old girls (the National Health Examination Survey), were analyzed by bivariate and multivariate analytic techniques for biologic, psychologic, and demographic correlates of dysmenorrhea. Of 1,611 adolescents (59,7%) who report dysmenorrhea, 14% frequently miss school because of cramps. The greatest proportion of variation of independent variables in a stepwise multiple regression analysis in this study was predicted by gynecologic or postmenarcheal age. Preparation for menarche, a psychologic variable, did not predict either dysmenorrhea or subsequent school absence. Socioeconomic status was positively correlated with dysmenorrhea although race was not. However, black students (23.6%) miss more school because of dysmenorrhea than white students (12.3%) even when socioeconomic status is held constant. Data in this study suggest that biologic variables play a substantial role in the pathogenesis of dysmenorrhea.

Absenteeism↗

Abrogation of genetically controlled resistance of mice to Treponema pallidum by irradiation.

Infection with Treponema pallidum, the causative agent of human syphilis, gives rise to a complex immune response involving both humoral and cellular components. The exact nature of this response and how it relates to the disease process is a matter of considerable speculation. In recent years, studies have been directed towards defining the role of cell-mediated immunity (CMI) in syphilis. These have been conducted mainly in vitro because the general unavailability of inbred rabbits, the principal animals for experimental syphilis research, has limited the application of in vivo procedures. A prime deterrent to using mice for the study of syphilis has been their failure to exhibit pathology, even in the face of a persistent infection. We report here that on intradermal (i.d.) infection, transient primary lesions, characteristic of those seen in naturally acquired human syphilis, can be produced regularly in some strains of mice but not others, indicating a genetic basis for host susceptibility. Strains of mice which normally fail to develop lesions, do so after exposure to ionising radiation. Evidence is presented for a multiple role of the immune response during local infection.

Animals↗

Update: adolescent gynecology.

As adolescents develop their sexual identities they are at risk for acquiring sexually transmitted diseases, unwanted pregnancies, and cervical dysplasia. As physical growth and development progress during adolescence, the risk of developing dysmenoorhea or adverse effects from exposure to diethylstilbestrol increase. The pediatrician with a background in growth and development should be capable of recognizing these conditions and participating in their management.

Adenocarcinoma↗

Functional heterogeneity of murine intestinal intraepithelial lymphocytes: studies using TCR-alpha beta+ IEL lines and fresh IEL isolates reveal multiple cytotoxic subsets differentiated by CD5, CD8 alpha/alpha, and CD8 alpha/beta expression.

Three T-cell lines, isolated from murine small intestine epithelia, have been studied with respect to phenotypic properties and cytotoxic activity. All lines were TCR-alpha beta+, Thy-1+, CD3+, CD4-, CD8+ but differed in that one line was CD8 alpha/alpha+, CD5-; one line was CD8 alpha/alpha+, CD5+; and one line was CD8 alpha/beta+, CD5+. Both the CD8 alpha/alpha+, CD5-, and the CD8 alpha/beta+, CD5+ lines lysed antigen-bearing target cells; however, the latter line also spontaneously lysed natural killer (NK)-sensitive target cells. The CD8 alpha/alpha+, CD5+ IEL line was nonlytic for antigen-bearing target cells, for NK-sensitive target cells, and in assays that detect lytic activity regardless of specificity. Three-color flow cytometric analyses of intestinal intraepithelial lymphocytes (IEL) in freshly-extracted preparations indicated that cells with the phenotypes of the three IEL lines are normally present in the murine intestine epithelium, and revealed considerable variability in the distribution and density of CD5 expression on murine IEL. In freshly extracted IEL depleted of CD5 or CD8 beta by cell sorting, cytotoxicity was found to reside both within the CD5+ and the CD5- IEL subsets, as well as in the CD8 beta-depleted (i.e., CD8 alpha/alpha+) subset. These findings demonstrate: that cytotoxicity of murine IEL resides among multiple phenotypic subsets; that the distribution and density of CD5 on IEL is more complex than previously described; and that T-cell lines of IEL origin are valuable for dissecting functional properties of specific IEL subsets, particularly those that constitute a small proportion of the total IEL.

Animals↗

Stimulation via the CD43 coreceptor augments T cell proliferation during the early phase of antigen-induced activation.

R2/60 is a monoclonal antibody (mAb) that recognizes the murine CD43 molecule expressed on mature T cells, developing thymocytes, and a subset of bone marrow hematopoietic stem cells. Recent studies using R2/60 demonstrate that CD43 is a costimulatory receptor involved in the activation of murine T cells. In the present study we have examined the kinetics of CD43-mediated costimulation in murine T cell populations including purified CD4+ and CD8+ peripheral T cells, and T cells activated in antigen-induced mixed-lymphocyte cultures. In each population, CD43 stimulation significantly enhanced T cell proliferation compared to non-CD43 activated cultures. CD43 costimulation was greatest in conjunction with suboptimal CD3 stimulation, and was most efficient during the early phase of antigen-driven activation, suggesting that under normal biologic conditions the role of CD43 may be to augment T cell responses early in immune activation.

Animals↗

T cell progenitors in the murine small intestine.

Lymphocytes in the murine small intestine epithelium are known to have a high proportion of extrathymic T cells. To explore the possibility that small intestine intraepithelial lymphocytes (IELs) are derived from T cell progenitors present within the intestine, intestine-derived cells with characteristics of early-stage T cell precursors were studied for their ability to regenerate IEL T cell populations following transfer into irradiated recipient mice. Cells within this population lacked markers of mature T cells but expressed heat-stable antigen, the c-kit receptor for stem cell factor, and/or the pre-T cell alpha gene. Upon adoptive transfer, donor cells preferentially homed to the intestine and did not repopulate the thymus or extraintestinal peripheral lymphoid tissues. IELs derived from the donor precursor pool included both (alpha beta and gamma delta T subsets and consisted of phenotypically heterogeneous cell populations defined by CD4 and CD8. These findings provide evidence that T cell progenitors located in the intestinal mucosa are the likely source of most intestinal IELs.

Animals↗