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. 1996 Nov 1;184(5):1725–1735. doi: 10.1084/jem.184.5.1725

Delayed maturation of CD4- CD8- Fc gamma RII/III+ T and natural killer cell precursors in Fc epsilon RI gamma transgenic mice

PMCID: PMC2192857  PMID: 8920861

Abstract

Fc epsilon RI gamma (gamma) is a member of a group of related proteins (the zeta-family dimers) that function as signal-transducing components of both Fc receptors and the T cell antigen receptor (TCR). Analysis of gamma expression during fetal thymus ontogeny revealed that it is expressed in early thymocytes, before the initiation of clonotypic TCR- alpha and TCR-beta gene rearrangement but is down-regulated in most adult thymocytes. To explore a possible role for gamma in thymocyte development, we generated transgenic mice in which this protein was overexpressed at all stages of ontogeny. Overexpression of gamma inhibited the maturation of T cells as well as natural killer (NK) cells. The developmental effects were transgene dose related and correlated with markedly delayed maturation of fetal CD4-CD8- FcRII/III+ thymocytes, cells thought to include the progenitors of both T and NK cells. These results suggest that the zeta and gamma chains serve distinctive functions in thymocyte development and indicate that Fc receptor(s) may play an important role in regulating the differentiation of early progenitor cells within the thymus.

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Selected References

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  1. Ernst L. K., Duchemin A. M., Anderson C. L. Association of the high-affinity receptor for IgG (Fc gamma RI) with the gamma subunit of the IgE receptor. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6023–6027. doi: 10.1073/pnas.90.13.6023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Fink P. J., Matis L. A., McElligott D. L., Bookman M., Hedrick S. M. Correlations between T-cell specificity and the structure of the antigen receptor. Nature. 1986 May 15;321(6067):219–226. doi: 10.1038/321219a0. [DOI] [PubMed] [Google Scholar]
  3. Fowlkes B. J., Pardoll D. M. Molecular and cellular events of T cell development. Adv Immunol. 1989;44:207–264. doi: 10.1016/s0065-2776(08)60643-4. [DOI] [PubMed] [Google Scholar]
  4. Godfrey D. I., Zlotnik A. Control points in early T-cell development. Immunol Today. 1993 Nov;14(11):547–553. doi: 10.1016/0167-5699(93)90186-O. [DOI] [PubMed] [Google Scholar]
  5. Greaves D. R., Wilson F. D., Lang G., Kioussis D. Human CD2 3'-flanking sequences confer high-level, T cell-specific, position-independent gene expression in transgenic mice. Cell. 1989 Mar 24;56(6):979–986. doi: 10.1016/0092-8674(89)90631-4. [DOI] [PubMed] [Google Scholar]
  6. Hedrick S. M., Cohen D. I., Nielsen E. A., Davis M. M. Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature. 1984 Mar 8;308(5955):149–153. doi: 10.1038/308149a0. [DOI] [PubMed] [Google Scholar]
  7. Koyasu S., D'Adamio L., Arulanandam A. R., Abraham S., Clayton L. K., Reinherz E. L. T cell receptor complexes containing Fc epsilon RI gamma homodimers in lieu of CD3 zeta and CD3 eta components: a novel isoform expressed on large granular lymphocytes. J Exp Med. 1992 Jan 1;175(1):203–209. doi: 10.1084/jem.175.1.203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kruisbeek A. M. Development of alpha beta T cells. Curr Opin Immunol. 1993 Apr;5(2):227–234. doi: 10.1016/0952-7915(93)90009-h. [DOI] [PubMed] [Google Scholar]
  9. Kurosaki T., Gander I., Ravetch J. V. A subunit common to an IgG Fc receptor and the T-cell receptor mediates assembly through different interactions. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3837–3841. doi: 10.1073/pnas.88.9.3837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lanier L. L., Kipps T. J., Phillips J. H. Functional properties of a unique subset of cytotoxic CD3+ T lymphocytes that express Fc receptors for IgG (CD16/Leu-11 antigen). J Exp Med. 1985 Dec 1;162(6):2089–2106. doi: 10.1084/jem.162.6.2089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Letourneur O., Kennedy I. C., Brini A. T., Ortaldo J. R., O'Shea J. J., Kinet J. P. Characterization of the family of dimers associated with Fc receptors (Fc epsilon RI and Fc gamma RIII). J Immunol. 1991 Oct 15;147(8):2652–2656. [PubMed] [Google Scholar]
  12. Liu C. P., Ueda R., She J., Sancho J., Wang B., Weddell G., Loring J., Kurahara C., Dudley E. C., Hayday A. Abnormal T cell development in CD3-zeta-/- mutant mice and identification of a novel T cell population in the intestine. EMBO J. 1993 Dec;12(12):4863–4875. doi: 10.1002/j.1460-2075.1993.tb06176.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Love P. E., Shores E. W., Johnson M. D., Tremblay M. L., Lee E. J., Grinberg A., Huang S. P., Singer A., Westphal H. T cell development in mice that lack the zeta chain of the T cell antigen receptor complex. Science. 1993 Aug 13;261(5123):918–921. doi: 10.1126/science.7688481. [DOI] [PubMed] [Google Scholar]
  14. Love P. E., Shores E. W., Lee E. J., Grinberg A., Munitz T. I., Westphal H., Singer A. Differential effects of zeta and eta transgenes on early alpha/beta T cell development. J Exp Med. 1994 May 1;179(5):1485–1494. doi: 10.1084/jem.179.5.1485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Malissen M., Gillet A., Rocha B., Trucy J., Vivier E., Boyer C., Köntgen F., Brun N., Mazza G., Spanopoulou E. T cell development in mice lacking the CD3-zeta/eta gene. EMBO J. 1993 Nov;12(11):4347–4355. doi: 10.1002/j.1460-2075.1993.tb06119.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ohno H., Aoe T., Taki S., Kitamura D., Ishida Y., Rajewsky K., Saito T. Developmental and functional impairment of T cells in mice lacking CD3 zeta chains. EMBO J. 1993 Nov;12(11):4357–4366. doi: 10.1002/j.1460-2075.1993.tb06120.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Orloff D. G., Ra C. S., Frank S. J., Klausner R. D., Kinet J. P. Family of disulphide-linked dimers containing the zeta and eta chains of the T-cell receptor and the gamma chain of Fc receptors. Nature. 1990 Sep 13;347(6289):189–191. doi: 10.1038/347189a0. [DOI] [PubMed] [Google Scholar]
  18. Qian D., Sperling A. I., Lancki D. W., Tatsumi Y., Barrett T. A., Bluestone J. A., Fitch F. W. The gamma chain of the high-affinity receptor for IgE is a major functional subunit of the T-cell antigen receptor complex in gamma delta T lymphocytes. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11875–11879. doi: 10.1073/pnas.90.24.11875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ra C., Jouvin M. H., Kinet J. P. Complete structure of the mouse mast cell receptor for IgE (Fc epsilon RI) and surface expression of chimeric receptors (rat-mouse-human) on transfected cells. J Biol Chem. 1989 Sep 15;264(26):15323–15327. [PubMed] [Google Scholar]
  20. Reth M. Antigen receptor tail clue. Nature. 1989 Mar 30;338(6214):383–384. doi: 10.1038/338383b0. [DOI] [PubMed] [Google Scholar]
  21. Rodewald H. R., Awad K., Moingeon P., D'Adamio L., Rabinowitz D., Shinkai Y., Alt F. W., Reinherz E. L. Fc gamma RII/III and CD2 expression mark distinct subpopulations of immature CD4-CD8- murine thymocytes: in vivo developmental kinetics and T cell receptor beta chain rearrangement status. J Exp Med. 1993 Apr 1;177(4):1079–1092. doi: 10.1084/jem.177.4.1079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rodewald H. R., Moingeon P., Lucich J. L., Dosiou C., Lopez P., Reinherz E. L. A population of early fetal thymocytes expressing Fc gamma RII/III contains precursors of T lymphocytes and natural killer cells. Cell. 1992 Apr 3;69(1):139–150. doi: 10.1016/0092-8674(92)90125-v. [DOI] [PubMed] [Google Scholar]
  23. Salcedo T. W., Kurosaki T., Kanakaraj P., Ravetch J. V., Perussia B. Physical and functional association of p56lck with Fc gamma RIIIA (CD16) in natural killer cells. J Exp Med. 1993 May 1;177(5):1475–1480. doi: 10.1084/jem.177.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sandor M., Galon J., Takacs L., Tatsumi Y., Mueller A. L., Sautes C., Lynch R. G. An alternative Fc gamma-receptor ligand: potential role in T-cell development. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12857–12861. doi: 10.1073/pnas.91.26.12857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Scholl P. R., Geha R. S. Physical association between the high-affinity IgG receptor (Fc gamma RI) and the gamma subunit of the high-affinity IgE receptor (Fc epsilon RI gamma). Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8847–8850. doi: 10.1073/pnas.90.19.8847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sánchez M. J., Muench M. O., Roncarolo M. G., Lanier L. L., Phillips J. H. Identification of a common T/natural killer cell progenitor in human fetal thymus. J Exp Med. 1994 Aug 1;180(2):569–576. doi: 10.1084/jem.180.2.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Takai T., Li M., Sylvestre D., Clynes R., Ravetch J. V. FcR gamma chain deletion results in pleiotrophic effector cell defects. Cell. 1994 Feb 11;76(3):519–529. doi: 10.1016/0092-8674(94)90115-5. [DOI] [PubMed] [Google Scholar]
  28. Teh H. S., Kisielow P., Scott B., Kishi H., Uematsu Y., Blüthmann H., von Boehmer H. Thymic major histocompatibility complex antigens and the alpha beta T-cell receptor determine the CD4/CD8 phenotype of T cells. Nature. 1988 Sep 15;335(6187):229–233. doi: 10.1038/335229a0. [DOI] [PubMed] [Google Scholar]
  29. Unkeless J. C. Characterization of a monoclonal antibody directed against mouse macrophage and lymphocyte Fc receptors. J Exp Med. 1979 Sep 19;150(3):580–596. doi: 10.1084/jem.150.3.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Vivier E., Rochet N., Kochan J. P., Presky D. H., Schlossman S. F., Anderson P. Structural similarity between Fc receptors and T cell receptors. Expression of the gamma-subunit of Fc epsilon RI in human T cells, natural killer cells and thymocytes. J Immunol. 1991 Dec 15;147(12):4263–4270. [PubMed] [Google Scholar]
  31. Wang B., Biron C., She J., Higgins K., Sunshine M. J., Lacy E., Lonberg N., Terhorst C. A block in both early T lymphocyte and natural killer cell development in transgenic mice with high-copy numbers of the human CD3E gene. Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9402–9406. doi: 10.1073/pnas.91.20.9402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Weiss A., Littman D. R. Signal transduction by lymphocyte antigen receptors. Cell. 1994 Jan 28;76(2):263–274. doi: 10.1016/0092-8674(94)90334-4. [DOI] [PubMed] [Google Scholar]
  33. Zúiga-Pflücker J. C., Schwartz H. L., Lenardo M. J. Gene transcription in differentiating immature T cell receptor(neg) thymocytes resembles antigen-activated mature T cells. J Exp Med. 1993 Oct 1;178(4):1139–1149. doi: 10.1084/jem.178.4.1139. [DOI] [PMC free article] [PubMed] [Google Scholar]

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