Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1996 Feb 1;183(2):589–598. doi: 10.1084/jem.183.2.589

Impaired primary T cell responses in L-selectin-deficient mice

PMCID: PMC2192435  PMID: 8627170

Abstract

L-selectin is a homing receptor that mediates the selective attachment of leukocytes to specialized high endothelial venules. To study the potential role of L-selectin in immune responses in intact mice, we generated L-selectin-deficient mice by gene targeting. L-selectin- deficient mice are defective in cutaneous delayed-type hypersensitivity (DTH) responses when tested after conventional intervals of immunization (4 d). Primary T cell proliferative responses and cytokine production (interleukin [IL] 2, IL-4, and interferon gamma) were also compromised when tested after 5 d of immunization, indicating that L- selectin is important for the immune response to antigens. In contrast, after more prolonged immunization protocols (9 d), normal responses were observed, suggesting that L-selectin-independent compensatory mechanisms exist. Interestingly, humoral responses of L-selectin- deficient mice to keyhole limpet hemocyanin are indistinguishable from wild-type control mice, implying that L-selectin plays no rate-limiting role in T cell help of B cell function. Thus, our results suggest that L-selectin plays an important role in the generation of primary T cell responses but may not be essential for humoral and memory T cell responses. L-selectin does not appear to be rate limiting for the events leading to antigen-driven neutrophil recruitment, since normal DTH responses are obtained at late time points after immunization.

Full Text

The Full Text of this article is available as a PDF (2.7 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arbonés M. L., Ord D. C., Ley K., Ratech H., Maynard-Curry C., Otten G., Capon D. J., Tedder T. F. Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin-deficient mice. Immunity. 1994 Jul;1(4):247–260. doi: 10.1016/1074-7613(94)90076-0. [DOI] [PubMed] [Google Scholar]
  2. Berg E. L., Goldstein L. A., Jutila M. A., Nakache M., Picker L. J., Streeter P. R., Wu N. W., Zhou D., Butcher E. C. Homing receptors and vascular addressins: cell adhesion molecules that direct lymphocyte traffic. Immunol Rev. 1989 Apr;108:5–18. doi: 10.1111/j.1600-065x.1989.tb00010.x. [DOI] [PubMed] [Google Scholar]
  3. Bradley L. M., Atkins G. G., Swain S. L. Long-term CD4+ memory T cells from the spleen lack MEL-14, the lymph node homing receptor. J Immunol. 1992 Jan 15;148(2):324–331. [PubMed] [Google Scholar]
  4. Bradley L. M., Duncan D. D., Yoshimoto K., Swain S. L. Memory effectors: a potent, IL-4-secreting helper T cell population that develops in vivo after restimulation with antigen. J Immunol. 1993 Apr 15;150(8 Pt 1):3119–3130. [PubMed] [Google Scholar]
  5. Bradley L. M., Watson S. R., Swain S. L. Entry of naive CD4 T cells into peripheral lymph nodes requires L-selectin. J Exp Med. 1994 Dec 1;180(6):2401–2406. doi: 10.1084/jem.180.6.2401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Butcher E. C. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell. 1991 Dec 20;67(6):1033–1036. doi: 10.1016/0092-8674(91)90279-8. [DOI] [PubMed] [Google Scholar]
  7. Butcher E. C. The regulation of lymphocyte traffic. Curr Top Microbiol Immunol. 1986;128:85–122. doi: 10.1007/978-3-642-71272-2_3. [DOI] [PubMed] [Google Scholar]
  8. Dailey M. O., Fathman C. G., Butcher E. C., Pillemer E., Weissman I. Abnormal migration of T lymphocyte clones. J Immunol. 1982 May;128(5):2134–2136. [PubMed] [Google Scholar]
  9. Dawson J., Sedgwick A. D., Edwards J. C., Lees P. The monoclonal antibody MEL-14 can block lymphocyte migration into a site of chronic inflammation. Eur J Immunol. 1992 Jun;22(6):1647–1650. doi: 10.1002/eji.1830220646. [DOI] [PubMed] [Google Scholar]
  10. Dowbenko D. J., Diep A., Taylor B. A., Lusis A. J., Lasky L. A. Characterization of the murine homing receptor gene reveals correspondence between protein domains and coding exons. Genomics. 1991 Feb;9(2):270–277. doi: 10.1016/0888-7543(91)90252-a. [DOI] [PubMed] [Google Scholar]
  11. Gallatin M., St John T. P., Siegelman M., Reichert R., Butcher E. C., Weissman I. L. Lymphocyte homing receptors. Cell. 1986 Mar 14;44(5):673–680. doi: 10.1016/0092-8674(86)90832-9. [DOI] [PubMed] [Google Scholar]
  12. Gallatin W. M., Weissman I. L., Butcher E. C. A cell-surface molecule involved in organ-specific homing of lymphocytes. Nature. 1983 Jul 7;304(5921):30–34. doi: 10.1038/304030a0. [DOI] [PubMed] [Google Scholar]
  13. Geoffroy J. S., Rosen S. D. Demonstration that a lectin-like receptor (gp90MEL) directly mediates adhesion of lymphocytes to high endothelial venules of lymph nodes. J Cell Biol. 1989 Nov;109(5):2463–2469. doi: 10.1083/jcb.109.5.2463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hamann A., Jablonski-Westrich D., Jonas P., Thiele H. G. Homing receptors reexamined: mouse LECAM-1 (MEL-14 antigen) is involved in lymphocyte migration into gut-associated lymphoid tissue. Eur J Immunol. 1991 Dec;21(12):2925–2929. doi: 10.1002/eji.1830211205. [DOI] [PubMed] [Google Scholar]
  15. Hou S., Doherty P. C. Partitioning of responder CD8+ T cells in lymph node and lung of mice with Sendai virus pneumonia by LECAM-1 and CD45RB phenotype. J Immunol. 1993 Jun 15;150(12):5494–5500. [PubMed] [Google Scholar]
  16. Jung T. M., Gallatin W. M., Weissman I. L., Dailey M. O. Down-regulation of homing receptors after T cell activation. J Immunol. 1988 Dec 15;141(12):4110–4117. [PubMed] [Google Scholar]
  17. Kamogawa Y., Minasi L. A., Carding S. R., Bottomly K., Flavell R. A. The relationship of IL-4- and IFN gamma-producing T cells studied by lineage ablation of IL-4-producing cells. Cell. 1993 Dec 3;75(5):985–995. doi: 10.1016/0092-8674(93)90542-x. [DOI] [PubMed] [Google Scholar]
  18. Kanof M. E., James S. P. Leu-8 antigen expression is diminished during cell activation but does not correlate with effector function of activated T lymphocytes. J Immunol. 1988 Jun 1;140(11):3701–3706. [PubMed] [Google Scholar]
  19. Kishimoto T. K., Jutila M. A., Butcher E. C. Identification of a human peripheral lymph node homing receptor: a rapidly down-regulated adhesion molecule. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2244–2248. doi: 10.1073/pnas.87.6.2244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lepault F., Gagnerault M. C., Faveeuw C., Boitard C. Recirculation, phenotype and functions of lymphocytes in mice treated with monoclonal antibody MEL-14. Eur J Immunol. 1994 Dec;24(12):3106–3112. doi: 10.1002/eji.1830241229. [DOI] [PubMed] [Google Scholar]
  21. Mackay C. R., Marston W. L., Dudler L. Naive and memory T cells show distinct pathways of lymphocyte recirculation. J Exp Med. 1990 Mar 1;171(3):801–817. doi: 10.1084/jem.171.3.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mackay C. R. Migration pathways and immunologic memory among T lymphocytes. Semin Immunol. 1992 Feb;4(1):51–58. [PubMed] [Google Scholar]
  23. Morimoto C., Letvin N. L., Distaso J. A., Aldrich W. R., Schlossman S. F. The isolation and characterization of the human suppressor inducer T cell subset. J Immunol. 1985 Mar;134(3):1508–1515. [PubMed] [Google Scholar]
  24. Murakawa Y., Minami Y., Strober W., James S. P. Association of human lymph node homing receptor (Leu 8) with the TCR/CD3 complex. J Immunol. 1992 Mar 15;148(6):1771–1776. [PubMed] [Google Scholar]
  25. Picker L. J., Butcher E. C. Physiological and molecular mechanisms of lymphocyte homing. Annu Rev Immunol. 1992;10:561–591. doi: 10.1146/annurev.iy.10.040192.003021. [DOI] [PubMed] [Google Scholar]
  26. Pizcueta P., Luscinskas F. W. Monoclonal antibody blockade of L-selectin inhibits mononuclear leukocyte recruitment to inflammatory sites in vivo. Am J Pathol. 1994 Aug;145(2):461–469. [PMC free article] [PubMed] [Google Scholar]
  27. Springer T. A. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell. 1994 Jan 28;76(2):301–314. doi: 10.1016/0092-8674(94)90337-9. [DOI] [PubMed] [Google Scholar]
  28. Streeter P. R., Rouse B. T., Butcher E. C. Immunohistologic and functional characterization of a vascular addressin involved in lymphocyte homing into peripheral lymph nodes. J Cell Biol. 1988 Nov;107(5):1853–1862. doi: 10.1083/jcb.107.5.1853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tedder T. F., Steeber D. A., Pizcueta P. L-selectin-deficient mice have impaired leukocyte recruitment into inflammatory sites. J Exp Med. 1995 Jun 1;181(6):2259–2264. doi: 10.1084/jem.181.6.2259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Thomas K. R., Capecchi M. R. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell. 1987 Nov 6;51(3):503–512. doi: 10.1016/0092-8674(87)90646-5. [DOI] [PubMed] [Google Scholar]
  31. Watson S. R., Fennie C., Lasky L. A. Neutrophil influx into an inflammatory site inhibited by a soluble homing receptor-IgG chimaera. Nature. 1991 Jan 10;349(6305):164–167. doi: 10.1038/349164a0. [DOI] [PubMed] [Google Scholar]
  32. Woodruff J. J., Clarke L. M., Chin Y. H. Specific cell-adhesion mechanisms determining migration pathways of recirculating lymphocytes. Annu Rev Immunol. 1987;5:201–222. doi: 10.1146/annurev.iy.05.040187.001221. [DOI] [PubMed] [Google Scholar]
  33. Yednock T. A., Rosen S. D. Lymphocyte homing. Adv Immunol. 1989;44:313–378. doi: 10.1016/s0065-2776(08)60645-8. [DOI] [PubMed] [Google Scholar]

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

RESOURCES