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MAL DE M'ERE.

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Adolescent↗

Alkylation of tryptophan during deprotection of Tmob-protected carboxamide side chains.

Alkylation of tryptophan occurred during the synthesis of a 19-amino acid peptide of the following sequence: Tyr Ala Ala Gln Asn Arg Arg Gly Leu Asp Leu Leu Phe Trp Glu Gln Gly Gly Leu. Alkylation was found to occur during cleavage of the peptide from the solid support under acidic conditions in the presence of Tmob, which is used for protecting glutamine and asparagine. Presence of alkylated tryptophan was confirmed by mass spectrometry, HPLC and amino acid sequence analyses.

Alkylation↗

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↗

Human gamma delta T cells amplify IgE production by Epstein-Barr virus-activated B cells.

In summary, these data document that gamma delta T cells regulate B cell differentiation, antibody synthesis, and IgE secretion in EBV-activated B cells. The classical "helper" subset of CD4+ alpha beta T cells, although potent inducers of other Ig isotypes, are not as efficient in augmenting IgE synthesis. However, interactions between alpha beta and gamma delta cells enhance the IgE response further. The precise mechanism by which gamma delta T cells function to augment IgE secretion is under study. It will be important, for example, to determine whether gamma delta T cells, or products of these cells, directly regulate class switching or mediate the clonal expansion of IgE-expressing B cells. In this regard, we ruled out the possibility that IL-4 release alone could replace gamma delta cells in increasing IgE secretion. Finally, we think it is of potential interest that gamma delta cells migrate to skin epithelia as well as gastrointestinal and pulmonary mucosa, sites of invasion by parasitic organisms and contact with allergens. If gamma delta T cells were specifically activated, either directly or indirectly, by these foreign pathogens, then the data presented here might elucidate the cellular basis for the events leading to IgE secretion, a critical step in the immune response to both parasites and allergens.

B-Lymphocytes↗

Human immunodeficiency virus type-1 infection of homosexual men is accompanied by a decrease in circulating B cells.

As part of the multidisciplinary effort to characterize the natural history of human immunodeficiency virus type 1 (HIV-1) infection, the cell-surface phenotypes of lymphocytes from a cohort of homosexual men were analyzed in detail and related to clinical and laboratory parameters associated with HIV-1 infection. The present study represents a cross-sectional analysis of coded specimens from 153 homosexual men, of whom 74 were seronegative and 79 seropositive for HIV-1. Fewer circulating B lymphocytes (CD19+) were found in HIV-1-seropositive subjects relative to a seronegative reference group. HIV seropositivity was not associated with decreased numbers of CD8+ T cells or activated T cells, which suggests that the number of circulating B cells specifically decreased. In addition to CD19, B cells were measured by CD20 and CD21 in a subset of subjects, and decreases in circulating CD20+ and CD21+ B cells were also apparent in HIV-1-seropositive subjects. The decrease in B-cell numbers was present at the earliest stages of HIV-1 infection (asymptomatic, clinically silent) and became more pronounced at more advanced stages of HIV-1 infection. The absolute B-cell numbers correlated with absolute CD4+ cell numbers (r = 0.59, p less than 0.001). These data suggest that HIV-1 infection is associated with progressive, selective decreases in the numbers of circulating CD4+ T cells and B cells.

Antigens, CD↗

Specific triggering of gamma, delta T cells by K562 activates the gamma, delta T cell receptor and may regulate natural killer-like function.

Freshly isolated and resting gamma/delta T cell lines, although capable of lysing a variety of MHC-unrestricted targets, fail to lyse K562. Yet, the killing of K562 can be specifically induced by antibodies to CD3 or delta-chains. Although this phenomenon may be caused by redirected lysis, it also raised the possibility that K562 may possess ligands capable of specifically interacting with the gamma/delta receptor. We found that K562 specifically induced both CD3 and delta modulation as well as IL-2R expression and IL-2 production by gamma/delta cells, supporting the idea that the TCR-gamma/delta is specifically triggered by K562 cells. Moreover, although the gamma/delta cell clones lysed other target cells (e.g., Molt 4, U937, Jurkat etc.), these latter targets did not induce delta modulation or IL-2R expression. In addition, F(ab)2 anti-CD3 antibodies inhibited activated gamma/delta T cells from killing K562 but did not inhibit the lysis of the other targets. Taken together, these results suggest that gamma/delta cells lyse some targets by utilizing receptors (perhaps NK-like) distinct from the gamma/delta receptor. We also found that triggering of the gamma/delta receptor by K562 inhibited the capacity of resting gamma/delta to lyse Molt 4 cells under conditions in which the K562 cells were not lysed. These findings suggest that the gamma/delta receptor maybe directly involved in the lysis of certain targets (i.e., K562) and, importantly, may potentially regulate the function of NK-like receptors that are involved in the lysis of other targets.

Animals↗

A human CD4- T cell leukemia subclone with contact-dependent helper function.

Helper T lymphocytes provide a contact dependent signal to resting B cells that is required for optimal differentiation into Ig-secreting cells. The surface structure(s) on T cells that mediate helper function have not been identified but are known to be induced by T cell activation. A CD4- subclone of the Jurkat leukemic T cell line (D1.1) was isolated and found to be distinct from CD4+ Jurkat clones and a variety of other T and non-T cell leukemic lines in that coculture of D1.1 with resting B cells induced B cells to specifically express surface CD23 molecules, a marker of B cell activation. Furthermore, Jurkat D1.1 induced B cell proliferation and terminal B cell differentiation into IgG-secreting cells in the presence of T cell-dependent B cell mitogens. Similar to the helper effector function of activated T cells, the effects of Jurkat D1.1 were neither Ag nor MHC restricted. Paraformaldehyde fixed Jurkat D1.1 cells remained competent to activate B cells while D1.1 supernatants and diffusible factors were inactive. The effect of Jurkat D1.1 on B cell activation was distinct from that of rIL-4 and was not inhibited by antibodies to IL-4. Together these observations suggested that surface structures on D1.1 and not secreted factors, mediated contact-dependent helper effector function.

Antigens, CD↗

Replication of herpes simplex virus and cytomegalovirus in human leukocytes.

Human peripheral blood leukocytes, lymphocyte subpopulations, and hemic cell lines were examined for their ability to supprot HSV and CMV replication. Mitogen-stimulated mononuclear leukocytes, B lymphocytes, and T lymphcytes supported the replication of HSV to high titers over 3 to 5 days of infection. HSV replicated in unstimulated mononuclear leukocyte cultures of one of five donors, and to a limited degree in untreated B lymphocytes of three of five donors; HSV replication was not detected in unstimulated T lymphocytes (five donors). There was no evidence of enhanced uptake of 3H-thymidine in the untreated donor cells that replicated HSV. CMV replication was not detected during 9 to 10 days of infection in untreated or mitogen-treated mononuclear leukocytes and lymphocyte subpopulations from the same adult donors or in neonatal cord blood leukocytes. The ability of the cells to support HSV or CMV replication did not correlate with the presence of specific antiviral antibodies in the donor serum. HSV replication in B, T, and myeloid cell lines to high titers over 5 days of infection, whereas CMV failed to replicate in any of the hemic cell lines. A persistent HSV infection has been established in a T cell line (CEM) with high titers of infectious virus being produced concurrently with growth of the cells over the first 11 weeks of infection.

Antibodies, Viral↗

Characterization of a unique cell line (LAZ 221) from human acute lymphocytic ("null" cell) leukemia.

A unique human cell line designated LAZ 221 has been established from the peripheral blood of a patient with acute lymphocytic leukemia of the "null" cell type. The cell line does not possess the Epstein-Barr virus nuclear antigen and has a karyotype of 45,XX,-9,-12,+(9q12q). Both the established cell line and the patient's uncultured blast cells share the same phenotypic markers. They both lack T-cell markers. They fail to form sheep erythrocyte rosettes and do not react with T-cell-specific antisera (TH1-, HTL-), nor do they possess B-cell markers. They do not form rosettes with erythrocytes sensitized with complement, and they are surface immunoglobulin negative. However, they do possess an HLA-D-related glycoprotein complex of 23,000 to 30,000 daltons, an la-like antigen. Thus, LAZ 221 shares the phenotype of the patient's uncultured blasts and is a cell line representative of about 75% of all human acute lymphocytic leukemias. In this respect it differs from previously described human hematopoietic cell lines.

Adult↗

Private practice may be good for your health and well-being.

During the past decade, the growth in private practice has generated considerable debate in the social work profession on values and mission. Much of this debate has focused on whether social workers should enter private practice. Not as much research has been done on why social workers enter private practice. Using national random samples drawn from 1985 NASW membership records, this study compares the personal well-being of individuals who are in full-time private practice with the personal well-being of individuals who are in full-time agency practice. On all measures of personal well-being used in the study, workers in private practice fare significantly better than their colleagues in agency settings. The authors suggest that personal well-being may be one of the factors leading social workers into private practice. Additional implications also are suggested.

Burnout, Professional↗