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T Goodman

Publications and source records attributed to T Goodman.

At least 19 recordsLinked to original sources
PubMed1990

Extrathymic selection of TCR gamma delta + T cells by class II major histocompatibility complex molecules.

The influence of MHC antigens on TCR gamma delta usage in CD8+ intraepithelial lymphocytes (IELs) was examined using a pan-reactive and V delta 4 region-specific MAb. While an average of 30% of IELs from the majority of mice of various MHC haplotypes were V delta 4+, a 2-fold or greater percentage of IELs from H-2k mice were V delta 4+. Analysis of IELs from F1 mice indicated that the increase in TCRs using V delta 4 was likely to be the result of positive selection. The V delta 4 usage patterns of IELs from recombinant inbred strains and from mice recombinant within H-2 revealed that the increase in V delta 4 usage mapped to H-2 and required I-E expression. Moreover, selection of TCRs using V delta 4 occurred in chimeric mice in the absence of a thymus. The results demonstrate an extrathymic selective mechanism for gamma delta TCRs of CD8+ IELs and suggest that these cells may exhibit MHC class II-restricted antigen recognition.

Animals↗
PubMed1989

Intraepithelial lymphocytes. Anatomical site, not T cell receptor form, dictates phenotype and function.

The function and structure of the TCR proteins of intraepithelial lymphocytes (IEL) were examined using a panel of mAbs specific for TCR-gamma/delta. Three subsets of TCR-gamma/delta+ IEL could be detected with five mAbs, termed GL1-GL5. The mAbs were able to trigger lysis via crosslinking of the IEL TCR and all of the subsets were constitutively cytolytic. Immunoprecipitation of IEL TCR proteins revealed that the GL2 mAb reacted only with gamma, delta heterodimers containing high Mr delta chains, while the other mAbs precipitated all of the observed gamma and delta proteins. Two-color fluorescence analysis showed that the GL2+ subset was contained within the larger GL1+ subset. The GL3 and GL4 mAbs appear to be specific for all TCR-gamma/delta while GL2 was V delta 4 specific. Analysis of IEL for TCR-alpha/beta expression demonstrated that approximately 20% of B6 IEL were TCR-alpha/beta+. Interestingly, this population of IEL contained Thy-1- and CT1+ cells, indicating that the unique phenotype of IEL was not restricted to TCR-gamma/delta+ cells. Moreover, the TCR-alpha/beta+ IEL were also constitutively cytolytic, suggesting that the intestinal milieu was controlling the functional programming of IEL regardless of TCR type. The mAbs reported here as well as the ability to exploit the distinct phenotype of IEL should prove useful in determining the function of IEL and the TCR-gamma/delta.

Animals↗
PubMed1989

Distinct antigen receptor repertoires of two classes of murine epithelium-associated T cells.

T lymphocytes are found not only as recirculating cells in the lymphoid system, but also as immobile cells in certain epithelia. T-cell antigen receptors (TCR) of both alpha/beta and gamma/delta-heterodimer subtypes can exhibit an extremely high degree of diversity. The diversity of alpha/beta TCRs derives from the use of a large number of variable (V) gene segments, as well as junctional diversity generated during rearrangement of these segments, whereas the diversity of gamma/delta TCRs derives largely from junctional elements, with a smaller contribution from a limited number of V gene segments. Many T cells in the epidermal and intestinal epithelia of mice express TCR composed of gamma/delta heterodimers. We demonstrate here that gamma/delta TCRs of T cells in both these tissues are restricted in V gene usage, with different elements predominating. The TCR junctional diversity of epidermal T cells, however, is extremely limited, whereas that of intestinal T cells is extremely diverse. The distinctive features of these two populations suggest that they develop or are selected differently for particular tissue-specific functions.

Animals↗
PubMed1989

In vivo modulation of cytolytic activity and Thy-1 expression in TCR-gamma delta+ intraepithelial lymphocytes.

Although the functional aspects of the alpha beta T cell antigen receptor (TCR) found on most peripheral T cells are well described, the function of the gamma delta TCR remains unclear. Murine intraepithelial lymphocytes (IEL) of the small intestine are CD8+, express the gamma delta TCR, and are constitutively lytic. Fresh IEL from germ-free mice had no lytic activity. Moreover, whereas IEL from normal mice are 30 to 50 percent Thy-1+, IEL from germ-free did not express Thy-1. Acclimation of germ-free mice to nonsterile conditions resulted in the generation of Thy-1+ IEL and induction of lytic activity. Thus CD8+ TCR-gamma delta IEL were regulated by externally derived stimuli via a specific functional interaction between IEL and gut-associated antigens.

Animals↗
PubMed1989

Lymphocyte beta-adrenoreceptor density in patients with unipolar depression and normal controls.

Values of binding maximum (Bmax) and dissociation constant (Kd) of (-)3-[125I]iodocyanopindolol (ICYP) were determined in beta-adrenergic receptors of membranes of peripheral lymphocytes in 32 patients with unipolar depression (DSM-III-R) and 31 normal controls. Results were analyzed by a two-way Analysis of Covariance method. A significant difference was noted for group assignment (patient versus control, p less than 0.05). Mean Bmax (fmol ICYP bound/mg lymphocyte membrane fraction total protein) of patients was 31.9 +/- 3.84 (SE) and controls 46.3 +/- 3.92 (SE). A significant interaction was found between group membership and gender (p less than 0.05). In the female patient group (n = 14), mean Bmax was 30.5 +/- 5.79 (SE); in female controls, mean Bmax was 56.0 +/- 5.15 (SE). Differences between male patients and male controls were not significant. Mean values of Kd (pmol/liter) showed a trend for patient values to be lower than control values [69.0 +/- 13.66 (SE) versus 108.5 +/- 14.42 (SE), respectively]. A significant inverse relationship was noted between lymphocyte beta-receptor Bmax and frequency of panic attacks during the depressive episode in 18 patients (p = 0.05). No relationship was found between values of Kd and frequency of panic attacks in these patients. Thus, preliminary evidence is provided for relationships among altered beta-adrenergic receptor binding, gender, and indices of panic-anxiety in unipolar depressed patients.

Adult↗
PubMed1989

Lymphocyte beta-adrenoceptor/effector complex in aging and dementia of the Alzheimer type.

We examined density (Bmax), affinity (Kd), and norepinephrine (NE)-stimulated cyclic adenosine monophosphate (cAMP) generation of the beta-adrenergic receptor on lymphocytes in patients with dementia of the Alzheimer type (DAT, n = 13), in normal aged controls (AGED, n = 27), and in young controls (YOUNG, n = 21). Bmax (fmol/mg protein; mean +/- SD) was significantly lower in YOUNG (48.0 +/- 18.7) than in either AGED (64.8 +/- 22.3) or DAT (63.6 +/- 19.5, p less than 0.05). Receptor sensitivity, i.e., the fold increase of stimulated over basal cAMP generation (S/B), was higher in DAT (8.3 +/- 5.2) than in AGED (5.5 +/- 2.3) or YOUNG (5.4 +/- 2.6, p less than 0.07). This difference was due to a significant increase in S/B in female but not male DAT patients compared with AGED (p less than 0.05). There were no differences in levels of circulating NE between DAT and AGED, nor between sexes. Thus, the present data suggest that in this model of the postsynaptic beta-adrenergic receptor/effector complex, receptor sensitivity was increased in women with DAT.

Adult↗
PubMed1988

Expression of the gamma-delta T-cell receptor on intestinal CD8+ intraepithelial lymphocytes.

The vast majority of mature T lymphocytes in the peripheral blood and lymphoid organs use the CD3-associated alpha, beta T-cell receptor (TCR) heterodimer for antigen recognition. A second class of TCRs consists of disulphide-linked gamma and delta proteins that are also CD3-associated. A subset of early CD3+ fetal and adult CD4- 8- thymocytes express gamma, delta TCRs before alpha, beta TCRs are detectable. In addition, a minor (1-5%) subpopulation of peripheral T lymphocytes, and some spleen cells from nude mice express gamma, delta TCRs. Notably, dendritic epidermal cells have also been shown to express gamma, delta TCRs. All of these populations lack CD4 and CD8 molecules. We now report that most mature T cells residing in the murine intestinal epithelium express CD3-associated TCRs composed of gamma-chains disulphide-linked to a protein resembling the delta-chain. The striking feature of these intraepithelial lymphocytes (IEL) was that they were exclusively CD4-8+. In addition, approximately half of CD3-bearing IEL lacked detectable Thy-1 on the cell surface, which is unprecedented for murine T cells. In contrast to other CD8+ peripheral T cells, freshly isolated IEL could be induced to display cytolytic activity by engaging the CD3 molecule, indicating that activation had occurred in vivo. Thus, CD8+ IEL are a phenotypically diverse and anatomically restricted population of lymphocytes that use gamma-chain containing heterodimers for antigen recognition.

Animals↗
PubMed1987

Developmental sequence of T200 antigen modifications in murine T cells.

The T200 glycoproteins of T cells were analyzed at different stages of T cell development. Immunoprecipitation and analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that Lyt-2-L3T4-, and Lyt-2+L3T4+ thymocytes had similar T200 proteins, whereas Lyt-2+L3T4- and Lyt-2-L3T4+ thymocytes expressed a distinct set of T200 molecules. This result indicated a molecular switch in regulation of T200 protein expression upon differentiation of thymocytes to mature phenotype T cells. Further modifications were evident when the T200 proteins of peripheral T cell subsets were examined. In particular L3T4+ T cells expressed T200 proteins of m.w. 220,000, 200,000, and 175,000, whereas Lyt-2+ lymph node T cells expressed an additional T200 protein of m.w. 235,000. Antigenic differences in the T200 glyco-proteins of peripheral L3T4+ and Lyt-2+ T cells were also detected. The anti-B220 monoclonal antibody, 14.8, reacted with lymph node Lyt-2+ T cells but did not react with lymph node L3T4+T cells or with Lyt-2+L3T4- thymocytes. This finding demonstrated a lineage-specific modification of the T200 protein of Lyt-2+ T cells that occurred after exit of these cells from the thymus into peripheral lymphoid organs. This modification apparently occurred on the m.w. 235,000 and 220,000 proteins since these species were precipitated by 14.8, whereas the others were not. In vitro growth and activation also resulted in further T200 antigen alterations. The monoclonal antibody, RA3, which reacts with the B220 antigen of B cells but, unlike 14.8, does not react with any peripheral T cells, showed significant reactivity with Lyt-2+ cytotoxic T cell (CTL) clones but not with L3T4+ T helper cell clones. CTL clones were also 14.8+ but T helper cell clones were not. Immunoprecipitation by 14.8 and RA3 of T200 proteins from CTL clones yielded a single protein of m.w. 240,000 that co-migrated with the B cell form of T200. Overall, the results indicate the presence of developmentally regulated mechanisms that control T200 glycoprotein expression during T cell differentiation in the thymus and in peripheral lymphoid organs.

Animals↗