International Journal of Hematology

, Volume 83, Issue 1, pp 12–16 | Cite as

CD4+CD3-Cells Regulate the Organization of Lymphoid Tissue and T-Cell Memory for Antibody Responses

  • Peter J. L. Lane
  • Mi-Yeon Kim
  • Fabrina M. C. Gaspal
  • Fiona M. McConnell


This review highlights the role of a CD4+CD3- accessory cell in the development of organized lymphoid infrastructures as well as in the development of high-affinity antibody responses and T-cell memory. These 2 functions are linked in the development of the vertebrate immune system and are effected by the constitutive expression of 2 sets of tumor necrosis factor (TNF) family members. The expression of lymphotoxin α (LTα), LTβ, and TNF-α, which are closely linked genetically, affects the organization of lymphoid structures into B-cell and T-cell areas; the dual expression of OX40 ligand (TNFSF4) and CD30 ligand (TNFSF8) influences both the survival of T-cells within germinal centers and T-cell memory. IntJHematol. 2006;83:12-16. doi: 10.1532/IJH97.05117

Key words

CD4+CD3- cells Inducer cells CD30 OX40 Memory 


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  1. 1.
    Zapata A, Ameimiya CT. Phylogeny of lower vertebrates and their immunological structures. In: du Pasquier L, Litman GW, eds. Origin and Evolution of the Vertebrate Immune System. Berlin, Germany: Springer; 2000:67–110.CrossRefGoogle Scholar
  2. 2.
    Breitfeld D, Ohl L, Kremmer E, et al. Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J Exp Med. 2000;192: 1545–1552.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Kim CH, Rott LS, Clark-Lewis I, Campbell DJ, Wu L, Butcher EC. Subspecialization of CXCR5+T cells: B helper activity is focused in a germinal center-localized subset of CXCR5+ T cells. J Exp Med. 2001;193:1373–1382.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Fu YX, Chaplin DD. Development and maturation of secondary lymphoid tissues. Annu Rev Immunol. 1999;17:399–433.CrossRefPubMedGoogle Scholar
  5. 5.
    Gunn MD, Ngo VN, Ansel KM, Ekland EH, Cyster JG, Williams LT. A B-homing chemokine made in lymphoid follicles activates Burkitt’s lymphoma type receptor-1. Nature. 1998;391:799–802.CrossRefPubMedGoogle Scholar
  6. 6.
    Luther SA, Tang HL, Hyman PL, Farr AG, Cyster JG. Coexpres- sion of the chemokines ELC and SLC by T zone stromal cells and deletion of the ELC gene in the plt/plt mouse. Proc NatlAcad Sci U S A. 2000;97:12694–12699.CrossRefGoogle Scholar
  7. 7.
    Kim MY, Gaspal FM, Wiggett HE, et al. CD4+CD3- accessory cells costimulate primed CD4 T cells through OX40 and CD30 at sites where T cells collaborate with B cells. Immunity. 2003;18:643–654.CrossRefPubMedGoogle Scholar
  8. 8.
    Gaspal FMC, Kim M, McConnell FM, Raykundalia C, Bekiaris V, Lane PJL. Mice deficient in OX40 and CD30 signals lack memory antibody responses because of deficient CD4 T cell memory. J Immunol. 2005;174:3891–3896.CrossRefPubMedGoogle Scholar
  9. 9.
    Kopf M, Ruedl C, Schmitz N, et al. OX40-deficient mice are defective in Th cell proliferation but are competent in generating B cell and CTL responses after virus infection. Immunity. 1999;11:699–708.CrossRefPubMedGoogle Scholar
  10. 10.
    Murata K, Ishii N, Takano H, et al. Impairment of antigen-presenting cell function in mice lacking expression of OX40 ligand. J Exp Med. 2000;191:365–374.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Chen AI, McAdam AJ, Buhlmann JE, et al. Ox40-ligand has a critical costimulatory role in dendritic cell:T cell interactions. Immunity. 1999;11:689–698.CrossRefPubMedGoogle Scholar
  12. 12.
    Rogers PR, Song J, Gramaglia I, Killeen N, Croft M. OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4T cells. Immunity. 2001;15:445–455.CrossRefPubMedGoogle Scholar
  13. 13.
    Mebius RE. Organogenesis of lymphoid tissues. Nat Rev Immunol. 2003;3:292–303.CrossRefPubMedGoogle Scholar
  14. 14.
    Kim MY, Anderson G, White A, et al. OX40 ligand and CD30 ligand are expressed on adult but not neonatal CD4+CD3- inducer cells: evidence that IL-7 signals regulate CD30 ligand but not OX40 ligand expression. J Immunol. 2005;174:6686–6691.CrossRefPubMedGoogle Scholar
  15. 15.
    Koopman G, Haaksma AG, ten Velden J, Hack CE, Heeney JL. The relative resistance of HIV type 1-infected chimpanzees to AIDS correlates with the maintenance of follicular architecture and the absence of infiltration by CD8+ cytotoxic T lymphocytes. AIDS Res Hum Retroviruses. 1999;15:365–373.CrossRefPubMedGoogle Scholar
  16. 16.
    Burke AP, Anderson D, Mannan P, et al. Systemic lymphadeno- pathic histology in human immunodeficiency virus-1-seropositive drug addicts without apparent acquired immunodeficiency syndrome. Hum Pathol. 1994;25:248–256.CrossRefPubMedGoogle Scholar
  17. 17.
    Porwit A, Bottiger B, Pallesen G, Bodner A, Biberfeld P. Follicular involution in HIV lymphadenopathy: a morphometric study. Apmis. 1989;97:153–165.CrossRefPubMedGoogle Scholar
  18. 18.
    Ochs HD, Junker AK, Collier AC, Virant FS, Handsfield HH, Wedgwood RJ. Abnormal antibody responses in patients with persistent generalized lymphadenopathy. J Clin Immunol. 1988;8:57–63.CrossRefPubMedGoogle Scholar
  19. 19.
    Eberl G, Littman DR. Thymic origin of intestinal aβ T cells revealed by fate mapping of ROR-γt+ cells. Science. 2004;305:248–251.CrossRefPubMedGoogle Scholar
  20. 20.
    Mebius RE, Rennert P, Weissman IL. Developing lymph nodes collect CD4+CD3- LTβ+ cells that can differentiate to APC, NK cells, and follicular cells but not T or B cells. Immunity. 1997;7:493–504.CrossRefPubMedGoogle Scholar

Copyright information

©  The Japanese Society of Hematology 2006

Authors and Affiliations

  • Peter J. L. Lane
    • 1
  • Mi-Yeon Kim
    • 1
  • Fabrina M. C. Gaspal
    • 1
  • Fiona M. McConnell
    • 1
  1. 1.Centre for Immune Regulation, Institute for Biomedical ResearchBirmingham Medical SchoolBirminghamUK

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