PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of jexpmedHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
 
J Exp Med. 1987 October 1; 166(4): 1168–1173.
PMCID: PMC2188714

Rearrangement and expression of T cell receptor genes in cloned murine natural suppressor cell lines

Abstract

Naturally occurring suppressor cells of the in vitro mixed leukocyte culture reaction and of in vivo graft-vs.-host disease have been identified in the spleens of neonatal mice (1) and of adult mice recovering from total lymphoid irradiation (2), whole-body irradiation (3), and syngeneic marrow transplantation (4), or cyclophosphamide therapy (5). Using both positive and negative selection procedures, the suppressors were reported to be null lymphocytes that did not express mature macrophage surface markers, nor differentiate into mature macrophages in vitro, nor demonstrate natural killer (NK) activity (1). Subsequently, cloned lines of these natural suppressor (NS) cells were derived from either adult mice given total lymphoid irradiation (TLI) (2) or from neonates (6). The cloned NS cell lines expressed a surface phenotype (2, 6) similar to that reported previously for cloned NK cells (Thy-1(+), asialo-GM1(+), Ig(-), Lyt-1(-), Lyt-2(-), Ia(-), MAC-1(-)) (7-9). However, the NS cells did not show NK activity in the standard assay with YAC-1 target cells. The cloned NS lines suppressed the proliferation of responder cells and the generation of cytolytic cells in the mixed leukocyte reaction (MLR), and suppressed lethal graft-vs.-host disease in vivo (10, 11). In view of the unusual function and surface phenotype of the cells, the lineage of these cells remained unclear. To determine the lineage of the cloned NS cells, we searched for expression and rearrangement of the α and β chain genes of the T cell antigen receptor, as well as that of the γ chain gene. Studies of the phenotypically similar NK cell yielded conflicting results. Thus, cloned lines of murine NK cells were reported to have rearrangements of the β chain genes, and to express mRNA for all three chains (12). In contrast, freshly purified rat or human large granular lymphocytes (LGL) were shown to express only the 1.0 kb mRNA species of the β chain gene (13), indicative of D-J joining (14). Thus, some but not all cells with NK function express the T cell receptor and are members of the T cell lineage. The current report shows that the NS lines express full-length mRNA transcripts for the a and β chain of the T cell receptor, as well as the γ chain gene.

Full Text

The Full Text of this article is available as a PDF (353K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Oseroff A, Okada S, Strober S. Natural suppressor (NS) cells found in the spleen of neonatal mice and adult mice given total lymphoid irradiation (TLI) express the null surface phenotype. J Immunol. 1984 Jan;132(1):101–110. [PubMed]
  • Hertel-Wulff B, Okada S, Oseroff A, Strober S. In vitro propagation and cloning of murine natural suppressor (NS) cells. J Immunol. 1984 Nov;133(5):2791–2796. [PubMed]
  • Waer M, Ang KK, Van der Schueren E, Vandeputte M. Allogeneic bone marrow transplantation in mice after total lymphoid irradiation: influence of breeding conditions and strain of recipient mice. J Immunol. 1984 Feb;132(2):991–996. [PubMed]
  • Waer M, Ang KK, van der Schueren E, Vandeputte M. Increased incidence of murine graft-versus-host disease after allogeneic bone marrow transplantation by previous infusion of syngeneic bone marrow cells. Transplantation. 1984 Oct;38(4):396–400. [PubMed]
  • Segre M, Tomei E, Segre D. Cyclophosphamide-induced suppressor cells in mice: suppression of the antibody response in vitro and characterization of the effector cells. Cell Immunol. 1985 Apr 1;91(2):443–454. [PubMed]
  • Schwadron RB, Gandour DM, Strober S. Cloned natural suppressor cell lines derived from the spleens of neonatal mice. J Exp Med. 1985 Jul 1;162(1):297–310. [PMC free article] [PubMed]
  • Dennert G, Yogeeswaran G, Yamagata S. Cloned cell lines with natural killer activity. Specificity, function, and cell surface markers. J Exp Med. 1981 Mar 1;153(3):545–556. [PMC free article] [PubMed]
  • Nabel G, Bucalo LR, Allard J, Wigzell H, Cantor H. Multiple activities of a cloned cell line mediating natural killer cell function. J Exp Med. 1981 Jun 1;153(6):1582–1591. [PMC free article] [PubMed]
  • Brooks CG, Kuribayashi K, Sale GE, Henney CS. Characterization of five cloned murine cell lines showing high cytolytic activity against YAC-1 cells. J Immunol. 1982 May;128(5):2326–2335. [PubMed]
  • Schwadron RB, Strober S. Cloned natural suppressor cells derived from the neonatal spleen: in vitro action and lineage. Transplant Proc. 1987 Feb;19(1 Pt 1):533–535. [PubMed]
  • Hertel-Wulff B, Palathumpat V, Schwadron R, Strober S. Prevention of graft-versus-host disease by natural suppressor cells. Transplant Proc. 1987 Feb;19(1 Pt 1):536–539. [PubMed]
  • Ikuta K, Hattori M, Wake K, Kano S, Honjo T, Yodoi J, Minato N. Expression and rearrangement of the alpha, beta, and gamma chain genes of the T cell receptor in cloned murine large granular lymphocyte lines. No correlation with the cytotoxic spectrum. J Exp Med. 1986 Aug 1;164(2):428–442. [PMC free article] [PubMed]
  • Young HA, Ortaldo JR, Herberman RB, Reynolds CW. Analysis of T cell receptors in highly purified rat and human large granular lymphocytes (LGL): lack of functional 1.3 kb beta-chain mRNA. J Immunol. 1986 Apr 1;136(7):2701–2704. [PubMed]
  • Kavaler J, Davis MM, Chien Y. Localization of a T-cell receptor diversity-region element. Nature. 1984 Aug 2;310(5976):421–423. [PubMed]
  • Denhardt DT. A membrane-filter technique for the detection of complementary DNA. Biochem Biophys Res Commun. 1966 Jun 13;23(5):641–646. [PubMed]
  • Hedrick SM, Cohen DI, Nielsen EA, Davis MM. Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature. 1984 Mar 8;308(5955):149–153. [PubMed]
  • Feinberg AP, Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. [PubMed]
  • Hedrick SM, Nielsen EA, Kavaler J, Cohen DI, Davis MM. Sequence relationships between putative T-cell receptor polypeptides and immunoglobulins. Nature. 1984 Mar 8;308(5955):153–158. [PubMed]
  • Raulet DH, Garman RD, Saito H, Tonegawa S. Developmental regulation of T-cell receptor gene expression. Nature. 1985 Mar 7;314(6006):103–107. [PubMed]
  • Samelson LE, Lindsten T, Fowlkes BJ, van den Elsen P, Terhorst C, Davis MM, Germain RN, Schwartz RH. Expression of genes of the T-cell antigen receptor complex in precursor thymocytes. Nature. 315(6022):765–768. [PubMed]
  • Saito H, Kranz DM, Takagaki Y, Hayday AC, Eisen HN, Tonegawa S. Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences. Nature. 309(5971):757–762. [PubMed]
  • Kranz DM, Saito H, Heller M, Takagaki Y, Haas W, Eisen HN, Tonegawa S. Limited diversity of the rearranged T-cell gamma gene. Nature. 313(6005):752–755. [PubMed]
  • Jones B, Mjolsness S, Janeway C, Jr, Hayday AC. Transcripts of functionally rearranged gamma genes in primary T cells of adult immunocompetent mice. Nature. 1986 Oct 16;323(6089):635–638. [PubMed]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press