Neoplastic Model for the Differentiation of a Subpopulation of Lymphocytes Bearing IgH‐1‐Linked Gene Products

Owen, Frances L.; Peterman, Gary M.

doi:10.1111/j.1600-065x.1984.tb01116.x

Cited by 6 publications

(3 citation statements)

References 27 publications

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“…Evidence suggests that α 1 PI also participates in hematopoiesis, specifically thymopoiesis [13]. During thymopoiesis, a cluster of mouse genes are expressed sequentially and were previously identified to encode the T cell alloantigens, Tpre, Tthy, Tind, and Tsu [14]. The chromosomal location of these maturational markers corresponds to that of α 1 PI, and using monoclonal antibodies that discriminate these mouse maturational markers, the human equivalent was identified as α 1 PI [15].…”

Section: Introductionmentioning

confidence: 99%

α1Proteinase Inhibitor Regulates CD4+ Lymphocyte Levels and Is Rate Limiting in HIV-1 Disease

et al. 2012

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BackgroundThe regulation of adult stem cell migration through human hematopoietic tissue involves the chemokine CXCL12 (SDF-1) and its receptor CXCR4 (CD184). In addition, human leukocyte elastase (HLE) plays a key role. When HLE is located on the cell surface (HLECS), it acts not as a proteinase, but as a receptor for α1proteinase inhibitor (α1PI, α1antitrypsin, SerpinA1). Binding of α1PI to HLECS forms a motogenic complex. We previously demonstrated that α1PI deficiency attends HIV-1 disease and that α1PI augmentation produces increased numbers of immunocompetent circulating CD4+ lymphocytes. Herein we investigated the mechanism underlying the α1PI deficiency that attends HIV-1 infection.Methods and FindingsActive α1PI in HIV-1 subjects (median 17 µM, n = 35) was significantly below normal (median 36 µM, p<0.001, n = 30). In HIV-1 uninfected subjects, CD4+ lymphocytes were correlated with the combined factors α1PI, HLECS + lymphocytes, and CXCR4+ lymphocytes (r2 = 0.91, p<0.001, n = 30), but not CXCL12. In contrast, in HIV-1 subjects with >220 CD4 cells/µl, CD4+ lymphocytes were correlated solely with active α1PI (r2 = 0.93, p<0.0001, n = 26). The monoclonal anti-HIV-1 gp120 antibody 3F5 present in HIV-1 patient blood is shown to bind and inactivate human α1PI. Chimpanzee α1PI differs from human α1PI by a single amino acid within the 3F5-binding epitope. Unlike human α1PI, chimpanzee α1PI did not bind 3F5 or become depleted following HIV-1 challenge, consistent with the normal CD4+ lymphocyte levels and benign syndrome of HIV-1 infected chimpanzees. The presence of IgG-α1PI immune complexes correlated with decreased CD4+ lymphocytes in HIV-1 subjects.ConclusionsThis report identifies an autoimmune component of HIV-1 disease that can be overcome therapeutically. Importantly, results identify an achievable vaccine modification with the novel objective to protect against AIDS as opposed to the current objective to protect against HIV-1 infection.

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Section: Introductionmentioning

confidence: 99%

α1Proteinase Inhibitor Regulates CD4+ Lymphocyte Levels and Is Rate Limiting in HIV-1 Disease

et al. 2012

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“…These surface antigens are encoded by the Tsu gene linkage group adjacent to the immunoglobulin heavy chain genes on murine chromosome 12 (9). Although these antigens have been identified on the surface of functional suppressor T cells (10)(11)(12), the physiological role of other T cells that express them has not been determined. As they mature, the T cells in this subclass express these antigens in a developmentally controlled sequence.…”

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confidence: 99%

“…The tumors that arise spontaneously in AKR mice (14,15) are derived from the subset of T cells that expresses Tsu linkage group antigens (9,12). These tumors appear to arise by the malignant transformation of individual cells at various stages in the maturation pathway of T cells (16).…”

mentioning

confidence: 99%

AKR murine thymic leukemias are from a distinct thymic cell lineage and do not express the beta chain of the T-cell antigen receptor.

Owen¹,

Strauss²,

Murre³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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AKR murine thymic leukemias are from a distinct thymic cell lineage and do not express the f3 chain of the T-cell antigen receptor (DNA ABSTRACT Characterization of tumors that arise spontaneously in the AKR Mouse indicates that they are derived from cells of a distinct T-cell lineage. Cells in this subclass bear surface antigens, designated Tpre, Tthy, Tind, and Tsu, which are encoded by genes in the Tsu linkage group on murine chromosome 12. We have examined the rearrangement and expression of genes encoding the T-cell a, (3, and y chains in these tumors. Although these cells contain a-chain mRNA, they do not produce a normal-sized fl-chain mRNA. Most of them also lack -chain mRNA. Each thymic leukemia was derived from a cell arrested at a different stage of development as dermed by their expression of terminal deoxynucleotidyl transferase and Thy-i mRNA. The data presented here are consistent with a model in which thymocytes expressing Tpre, Tthy, Tind, or Tsu undergo somatic development parallel to the development ofother T cells. However, these thymocytes do not appear to differentiate into cells bearing a-f heterodimers of the T-cell antigen receptor.

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Tind, Tsu and Tthy form a Trimolecular Complex Encoded Within the Tsu Locus on Chromosome 12 of the Mouse

Peterman

Singhai

Dean

et al. 1988

Genetics of Immunological Diseases

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Neoplastic Model for the Differentiation of a Subpopulation of Lymphocytes Bearing IgH‐1‐Linked Gene Products

Cited by 6 publications

References 27 publications

α1Proteinase Inhibitor Regulates CD4+ Lymphocyte Levels and Is Rate Limiting in HIV-1 Disease

α1Proteinase Inhibitor Regulates CD4+ Lymphocyte Levels and Is Rate Limiting in HIV-1 Disease

AKR murine thymic leukemias are from a distinct thymic cell lineage and do not express the beta chain of the T-cell antigen receptor.

Tind, Tsu and Tthy form a Trimolecular Complex Encoded Within the Tsu Locus on Chromosome 12 of the Mouse

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