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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Jun 6;92(12):5689–5693. doi: 10.1073/pnas.92.12.5689

Blockade of T- and B-lymphocyte development by antibody to the gamma c subunit of the receptors for interleukins 2, 4, and 7.

Y W He 1, R B Levy 1, T R Malek 1
PMCID: PMC41762  PMID: 7777571

Abstract

Cytokines are important regulators of hematopoesis. Mutations in gamma c, which is a subunit shared by the receptors for interleukin (IL) 2, IL-4, and IL-7, have been causally associated with human X chromosome-linked severe combined immunodeficiency disease. This finding indicates a mandatory role for cytokine receptor signaling at one or more stages of lymphocyte development. To evaluate the cellular level at which gamma c is critical for lymphopoiesis, the effect of monoclonal antibodies to gamma c on the capacity of syngeneic bone marrow cells to reconstitute the hematopoietic compartment of lethally irradiated recipient mice was examined. We show that monoclonal antibody to gamma c blocked lymphocyte development at or before the appearance of pro-B cells and prior to or at the seeding of the thymus by precursor cells while erythromyeloid cell development was normal. These results suggest that one level of lymphocyte development that requires gamma c is a point in hematopoietic cell differentiation near the divergence of lymphopoiesis and erythromyelopoesis.

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Selected References

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  1. Asao H., Takeshita T., Ishii N., Kumaki S., Nakamura M., Sugamura K. Reconstitution of functional interleukin 2 receptor complexes on fibroblastoid cells: involvement of the cytoplasmic domain of the gamma chain in two distinct signaling pathways. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4127–4131. doi: 10.1073/pnas.90.9.4127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cao X., Shores E. W., Hu-Li J., Anver M. R., Kelsall B. L., Russell S. M., Drago J., Noguchi M., Grinberg A., Bloom E. T. Defective lymphoid development in mice lacking expression of the common cytokine receptor gamma chain. Immunity. 1995 Mar;2(3):223–238. doi: 10.1016/1074-7613(95)90047-0. [DOI] [PubMed] [Google Scholar]
  3. Coffman R. L., Weissman I. L. A monoclonal antibody that recognizes B cells and B cell precursors in mice. J Exp Med. 1981 Feb 1;153(2):269–279. doi: 10.1084/jem.153.2.269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Conley M. E., Lavoie A., Briggs C., Brown P., Guerra C., Puck J. M. Nonrandom X chromosome inactivation in B cells from carriers of X chromosome-linked severe combined immunodeficiency. Proc Natl Acad Sci U S A. 1988 May;85(9):3090–3094. doi: 10.1073/pnas.85.9.3090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. DiSanto J. P., Dautry-Varsat A., Certain S., Fischer A., de Saint Basile G. Interleukin-2 (IL-2) receptor gamma chain mutations in X-linked severe combined immunodeficiency disease result in the loss of high-affinity IL-2 receptor binding. Eur J Immunol. 1994 Feb;24(2):475–479. doi: 10.1002/eji.1830240232. [DOI] [PubMed] [Google Scholar]
  6. DiSanto J. P., Müller W., Guy-Grand D., Fischer A., Rajewsky K. Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain. Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):377–381. doi: 10.1073/pnas.92.2.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fleming T. J., Fleming M. L., Malek T. R. Selective expression of Ly-6G on myeloid lineage cells in mouse bone marrow. RB6-8C5 mAb to granulocyte-differentiation antigen (Gr-1) detects members of the Ly-6 family. J Immunol. 1993 Sep 1;151(5):2399–2408. [PubMed] [Google Scholar]
  8. Giri J. G., Ahdieh M., Eisenman J., Shanebeck K., Grabstein K., Kumaki S., Namen A., Park L. S., Cosman D., Anderson D. Utilization of the beta and gamma chains of the IL-2 receptor by the novel cytokine IL-15. EMBO J. 1994 Jun 15;13(12):2822–2830. doi: 10.1002/j.1460-2075.1994.tb06576.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Grabstein K. H., Waldschmidt T. J., Finkelman F. D., Hess B. W., Alpert A. R., Boiani N. E., Namen A. E., Morrissey P. J. Inhibition of murine B and T lymphopoiesis in vivo by an anti-interleukin 7 monoclonal antibody. J Exp Med. 1993 Jul 1;178(1):257–264. doi: 10.1084/jem.178.1.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hardy R. R., Carmack C. E., Shinton S. A., Kemp J. D., Hayakawa K. Resolution and characterization of pro-B and pre-pro-B cell stages in normal mouse bone marrow. J Exp Med. 1991 May 1;173(5):1213–1225. doi: 10.1084/jem.173.5.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. He Y. W., Adkins B., Furse R. K., Malek T. R. Expression and function of the gamma c subunit of the IL-2, IL-4, and IL-7 receptors. Distinct interaction of gamma c in the IL-4 receptor. J Immunol. 1995 Feb 15;154(4):1596–1605. [PubMed] [Google Scholar]
  12. Jones M. S., Riley R., Hamilton B. L., Paupe J., Perez D., Levy R. B. Endogenous superantigens in allogeneic bone marrow transplant recipients rapidly and selectively expand donor T cells which can produce IFN-gamma. Bone Marrow Transplant. 1994 Nov;14(5):725–735. [PubMed] [Google Scholar]
  13. Kondo M., Takeshita T., Higuchi M., Nakamura M., Sudo T., Nishikawa S., Sugamura K. Functional participation of the IL-2 receptor gamma chain in IL-7 receptor complexes. Science. 1994 Mar 11;263(5152):1453–1454. doi: 10.1126/science.8128231. [DOI] [PubMed] [Google Scholar]
  14. Kondo M., Takeshita T., Ishii N., Nakamura M., Watanabe S., Arai K., Sugamura K. Sharing of the interleukin-2 (IL-2) receptor gamma chain between receptors for IL-2 and IL-4. Science. 1993 Dec 17;262(5141):1874–1877. doi: 10.1126/science.8266076. [DOI] [PubMed] [Google Scholar]
  15. Kopf M., Le Gros G., Bachmann M., Lamers M. C., Bluethmann H., Köhler G. Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature. 1993 Mar 18;362(6417):245–248. doi: 10.1038/362245a0. [DOI] [PubMed] [Google Scholar]
  16. Leo O., Foo M., Sachs D. H., Samelson L. E., Bluestone J. A. Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1374–1378. doi: 10.1073/pnas.84.5.1374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Leonard W. J., Noguchi M., Russell S. M., McBride O. W. The molecular basis of X-linked severe combined immunodeficiency: the role of the interleukin-2 receptor gamma chain as a common gamma chain, gamma c. Immunol Rev. 1994 Apr;138:61–86. doi: 10.1111/j.1600-065x.1994.tb00847.x. [DOI] [PubMed] [Google Scholar]
  18. Malek T. R., Shevach E. M., Danis K. M. Activation of T lymphocytes through the Ly-6 pathway is defective in A strain mice. J Immunol. 1989 Jul 15;143(2):439–445. [PubMed] [Google Scholar]
  19. Noguchi M., Nakamura Y., Russell S. M., Ziegler S. F., Tsang M., Cao X., Leonard W. J. Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor. Science. 1993 Dec 17;262(5141):1877–1880. doi: 10.1126/science.8266077. [DOI] [PubMed] [Google Scholar]
  20. Noguchi M., Yi H., Rosenblatt H. M., Filipovich A. H., Adelstein S., Modi W. S., McBride O. W., Leonard W. J. Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans. Cell. 1993 Apr 9;73(1):147–157. doi: 10.1016/0092-8674(93)90167-o. [DOI] [PubMed] [Google Scholar]
  21. Peschon J. J., Morrissey P. J., Grabstein K. H., Ramsdell F. J., Maraskovsky E., Gliniak B. C., Park L. S., Ziegler S. F., Williams D. E., Ware C. B. Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J Exp Med. 1994 Nov 1;180(5):1955–1960. doi: 10.1084/jem.180.5.1955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Puck J. M. X-linked immunodeficiencies. Adv Hum Genet. 1993;21:107–144. doi: 10.1007/978-1-4615-3010-7_2. [DOI] [PubMed] [Google Scholar]
  23. Russell S. M., Keegan A. D., Harada N., Nakamura Y., Noguchi M., Leland P., Friedmann M. C., Miyajima A., Puri R. K., Paul W. E. Interleukin-2 receptor gamma chain: a functional component of the interleukin-4 receptor. Science. 1993 Dec 17;262(5141):1880–1883. doi: 10.1126/science.8266078. [DOI] [PubMed] [Google Scholar]
  24. Sadlack B., Kühn R., Schorle H., Rajewsky K., Müller W., Horak I. Development and proliferation of lymphocytes in mice deficient for both interleukins-2 and -4. Eur J Immunol. 1994 Jan;24(1):281–284. doi: 10.1002/eji.1830240144. [DOI] [PubMed] [Google Scholar]
  25. Schorle H., Holtschke T., Hünig T., Schimpl A., Horak I. Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting. Nature. 1991 Aug 15;352(6336):621–624. doi: 10.1038/352621a0. [DOI] [PubMed] [Google Scholar]
  26. Sudo T., Nishikawa S., Ohno N., Akiyama N., Tamakoshi M., Yoshida H., Nishikawa S. Expression and function of the interleukin 7 receptor in murine lymphocytes. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9125–9129. doi: 10.1073/pnas.90.19.9125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Takeshita T., Asao H., Ohtani K., Ishii N., Kumaki S., Tanaka N., Munakata H., Nakamura M., Sugamura K. Cloning of the gamma chain of the human IL-2 receptor. Science. 1992 Jul 17;257(5068):379–382. doi: 10.1126/science.1631559. [DOI] [PubMed] [Google Scholar]
  28. Tanaka T., Takeuchi Y., Shiohara T., Kitamura F., Nagasaka Y., Hamamura K., Yagita H., Miyasaka M. In utero treatment with monoclonal antibody to IL-2 receptor beta-chain completely abrogates development of Thy-1+ dendritic epidermal cells. Int Immunol. 1992 Apr;4(4):487–491. doi: 10.1093/intimm/4.4.487. [DOI] [PubMed] [Google Scholar]
  29. Tentori L., Longo D. L., Zuñiga-Pflucker J. C., Wing C., Kruisbeek A. M. Essential role of the interleukin 2-interleukin 2 receptor pathway in thymocyte maturation in vivo. J Exp Med. 1988 Nov 1;168(5):1741–1747. doi: 10.1084/jem.168.5.1741. [DOI] [PMC free article] [PubMed] [Google Scholar]

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