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PMID: 11581317 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Migratory properties of naive, effector, and memory CD8(+) T cells.

The Journal of experimental medicine ·Vol. 194 ·No. 7 ·2001-10-01 ·Pages 953-66

Weninger W, Crowley MA, Manjunath N, von Andrian UH

Abstract

It has been proposed that two different antigen-experienced T cell subsets may be distinguishable by their preferential ability to home to lymphoid organs (central memory cells) or nonlymphoid tissues (effector memory/effector cells). We have shown recently that murine antigen-primed CD8(+) T cells cultured in interleukin (IL)-15 (CD8(IL-15)) resemble central memory cells in phenotype and function. In contrast, primed CD8(+) T cells cultured in IL-2 (CD8(IL-2)) become cytotoxic effector cells. Here, the migratory behavior of these two subsets was investigated. Naive, CD8(IL-15) cells and, to a lesser degree, CD8(IL-2) cells localized to T cell areas in the spleen, but only naive and CD8(IL-15) cells homed to lymph nodes (LNs) and Peyer's patches. Intravital microscopy of peripheral LNs revealed that CD8(IL-15) cells, but not CD8(IL-2) cells, rolled and arrested in high endothelial venules (HEVs). Migration of CD8(IL-15) cells to LNs depended on L-selectin and required chemokines that bind CC chemokine receptor (CCR)7. Both antigen-experienced populations, but not naive T cells, responded to inflammatory chemokines and accumulated at sites of inflammation. However, CD8(IL-2) cells were 12 times more efficient in migrating to inflamed peritoneum than CD8(IL-15) cells. Furthermore, CD8(IL-15) cells proliferated rapidly upon reencounter with antigen at sites of inflammation. Thus, central memory-like CD8(IL-15) cells home avidly to lymphoid organs and moderately to sites of inflammation, where they mediate rapid recall responses, whereas CD8(IL-2) effector T cells accumulate in inflamed tissues, but are excluded from most lymphoid organs.

MeSH Terms
Animals Blood Circulation CD8-Positive T-Lymphocytes/immunology Cell Division Chemotaxis, Leukocyte/immunology Female Immunologic Memory Inflammation/immunology Interleukin-15/immunology Interleukin-2/immunology Lymph Nodes/cytology,immunology Lymphatic System/cytology,immunology Male Mice Peyer's Patches/cytology,immunology Spleen/cytology,immunology T-Lymphocyte Subsets/immunology
Chemicals
Interleukin-15 Interleukin-2
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Weninger W
The Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA.
Crowley M A
Manjunath N
von Andrian U H
References (62)
62 references, click to expand
  1. A cell-surface molecule involved in organ-specific homing of lymphocytes.
    Nature. 1983 Jul 7-13;304(5921):30-4 PMID: 6866086
  2. Intravital microscopy of the peripheral lymph node microcirculation in mice.
    Microcirculation. 1996 Sep;3(3):287-300 PMID: 8930886
  3. Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen.
    Nature. 1989 Nov 30;342(6249):559-61 PMID: 2573841
  4. Naive and memory T cells show distinct pathways of lymphocyte recirculation.
    J Exp Med. 1990 Mar 1;171(3):801-17 PMID: 2307933
  5. T-cell memory: the connection between function, phenotype and migration pathways.
    Immunol Today. 1991 Jun;12(6):189-92 PMID: 1831615
  6. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm.
    Cell. 1994 Jan 28;76(2):301-14 PMID: 7507411
  7. T and B memory cells.
    Cell. 1994 Jan 28;76(2):315-22 PMID: 8293465
  8. Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin-deficient mice.
    Immunity. 1994 Jul;1(4):247-60 PMID: 7534203
  9. Pertussis toxin inhibits migration of B and T lymphocytes into splenic white pulp cords.
    J Exp Med. 1995 Aug 1;182(2):581-6 PMID: 7629515
  10. Molecular pathways of CTL-mediated cytotoxicity.
    Immunol Rev. 1995 Aug;146:33-44 PMID: 7493758
  11. The route of antigen entry determines the requirement for L-selectin during immune responses.
    J Exp Med. 1996 Dec 1;184(6):2341-51 PMID: 8976188
  12. P- and E-selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into inflammed tissues.
    Nature. 1997 Jan 2;385(6611):81-3 PMID: 8985251
  13. Genetic defect in T lymphocyte-specific homing into peripheral lymph nodes.
    Eur J Immunol. 1997 Jan;27(1):215-21 PMID: 9022021
  14. P-selectin glycoprotein ligand-1 (PSGL-1) on T helper 1 but not on T helper 2 cells binds to P-selectin and supports migration into inflamed skin.
    J Exp Med. 1997 Feb 3;185(3):573-8 PMID: 9053457
  15. Dendritic cells in the T-cell areas of lymphoid organs.
    Immunol Rev. 1997 Apr;156:25-37 PMID: 9176697
  16. Homing of naive and memory T lymphocyte subsets to Peyer's patches, lymph nodes, and spleen.
    J Immunol. 1997 Aug 15;159(4):1746-52 PMID: 9257836
  17. The migratory behavior of murine CD4+ cells of memory phenotype.
    Eur J Immunol. 1997 Sep;27(9):2225-32 PMID: 9341763
  18. Requirement for CD44 in activated T cell extravasation into an inflammatory site.
    Science. 1997 Oct 24;278(5338):672-5 PMID: 9381175
  19. A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naive T lymphocytes.
    Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):258-63 PMID: 9419363
  20. Circulating activated platelets reconstitute lymphocyte homing and immunity in L-selectin-deficient mice.
    J Exp Med. 1998 Jan 19;187(2):197-204 PMID: 9432977
  21. Molecular mechanisms of lymphocyte homing to peripheral lymph nodes.
    J Exp Med. 1998 Jan 19;187(2):205-16 PMID: 9432978
  22. Dendritic cells and the control of immunity.
    Nature. 1998 Mar 19;392(6673):245-52 PMID: 9521319
  23. A novel mutant gene involved in T-lymphocyte-specific homing into peripheral lymphoid organs on mouse chromosome 4.
    Blood. 1998 Apr 15;91(8):2886-95 PMID: 9531599
  24. T cell memory.
    Annu Rev Immunol. 1998;16:201-23 PMID: 9597129
  25. Transendothelial migration and trafficking of leukocytes in LFA-1-deficient mice.
    Eur J Immunol. 1998 Jun;28(6):1959-69 PMID: 9645378
  26. Differentiation of naive CTL to effector and memory CTL: correlation of effector function with phenotype and cell division.
    J Immunol. 1998 Nov 15;161(10):5338-46 PMID: 9820507
  27. In situ analysis of lymphocyte migration to lymph nodes.
    Cell Adhes Commun. 1998;6(2-3):85-96 PMID: 9823458
  28. Core 2 oligosaccharide biosynthesis distinguishes between selectin ligands essential for leukocyte homing and inflammation.
    Immunity. 1998 Dec;9(6):881-90 PMID: 9881978
  29. Migration kinetics and final destination of type 1 and type 2 CD8 effector cells predict protection against pulmonary virus infection.
    J Exp Med. 1999 Jan 18;189(2):423-34 PMID: 9892624
  30. Mice lacking expression of secondary lymphoid organ chemokine have defects in lymphocyte homing and dendritic cell localization.
    J Exp Med. 1999 Feb 1;189(3):451-60 PMID: 9927507
  31. Lymphocyte migration in lymphocyte function-associated antigen (LFA)-1-deficient mice.
    J Exp Med. 1999 May 3;189(9):1467-78 PMID: 10224287
  32. Acquisition of selectin binding and peripheral homing properties by CD4(+) and CD8(+) T cells.
    J Exp Med. 1999 Jun 7;189(11):1765-76 PMID: 10359580
  33. CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs.
    Cell. 1999 Oct 1;99(1):23-33 PMID: 10520991
  34. The reduced expression of 6Ckine in the plt mouse results from the deletion of one of two 6Ckine genes.
    J Exp Med. 1999 Oct 18;190(8):1183-8 PMID: 10523616
  35. Immunological memory and protective immunity: understanding their relation.
    Science. 1996 Apr 5;272(5258):54-60 PMID: 8600537
  36. Lymphocyte homing and homeostasis.
    Science. 1996 Apr 5;272(5258):60-6 PMID: 8600538
  37. Molecular mechanisms of lymphocyte-mediated cytotoxicity and their role in immunological protection and pathogenesis in vivo.
    Annu Rev Immunol. 1996;14:207-32 PMID: 8717513
  38. The alpha(1,3)fucosyltransferase Fuc-TVII controls leukocyte trafficking through an essential role in L-, E-, and P-selectin ligand biosynthesis.
    Cell. 1996 Aug 23;86(4):643-53 PMID: 8752218
  39. How organ-specific is the migration of 'naive' and 'memory' T cells?
    Immunol Today. 1996 Jun;17(6):278-82 PMID: 8962631
  40. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions.
    Nature. 1999 Oct 14;401(6754):708-12 PMID: 10537110
  41. Distinct migration patterns of naive and effector CD8 T cells in the spleen: correlation with CCR7 receptor expression and chemokine reactivity.
    Eur J Immunol. 1999 Nov;29(11):3562-70 PMID: 10556810
  42. A transgenic mouse model to analyze CD8(+) effector T cell differentiation in vivo.
    Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13932-7 PMID: 10570176
  43. The role of CCR7 in TH1 and TH2 cell localization and delivery of B cell help in vivo.
    Science. 1999 Dec 10;286(5447):2159-62 PMID: 10591648
  44. The CC chemokine thymus-derived chemotactic agent 4 (TCA-4, secondary lymphoid tissue chemokine, 6Ckine, exodus-2) triggers lymphocyte function-associated antigen 1-mediated arrest of rolling T lymphocytes in peripheral lymph node high endothelial venules.
    J Exp Med. 2000 Jan 3;191(1):61-76 PMID: 10620605
  45. The role of chemokines in the microenvironmental control of T versus B cell arrest in Peyer's patch high endothelial venules.
    J Exp Med. 2000 Jan 3;191(1):77-88 PMID: 10620606
  46. Th1/Th2 subsets: distinct differences in homing and chemokine receptor expression?
    Springer Semin Immunopathol. 1999;21(3):263-85 PMID: 10666773
  47. Chemokines: a new classification system and their role in immunity.
    Immunity. 2000 Feb;12(2):121-7 PMID: 10714678
  48. Differentiating between memory and effector CD8 T cells by altered expression of cell surface O-glycans.
    J Exp Med. 2000 Apr 3;191(7):1241-6 PMID: 10748241
  49. Control of homeostasis of CD8+ memory T cells by opposing cytokines.
    Science. 2000 Apr 28;288(5466):675-8 PMID: 10784451
  50. The role of chemokine receptors in primary, effector, and memory immune responses.
    Annu Rev Immunol. 2000;18:593-620 PMID: 10837070
  51. Specialized contributions by alpha(1,3)-fucosyltransferase-IV and FucT-VII during leukocyte rolling in dermal microvessels.
    Immunity. 2000 Jun;12(6):665-76 PMID: 10894166
  52. CCR2+ and CCR5+ CD8+ T cells increase during viral infection and migrate to sites of infection.
    Eur J Immunol. 2000 Jul;30(7):1797-806 PMID: 10940868
  53. Functionally distinct CD8+ memory T cell subsets in persistent EBV infection are differentiated by migratory receptor expression.
    Eur J Immunol. 2000 Jul;30(7):1823-9 PMID: 10940871
  54. T-cell function and migration. Two sides of the same coin.
    N Engl J Med. 2000 Oct 5;343(14):1020-34 PMID: 11018170
  55. Coexpression of the chemokines ELC and SLC by T zone stromal cells and deletion of the ELC gene in the plt/plt mouse.
    Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12694-9 PMID: 11070085
  56. Activation induces rapid and profound alterations in the trafficking of T cells.
    Eur J Immunol. 2000 Nov;30(11):3207-18 PMID: 11093136
  57. CD8(+) but not CD8(-) dendritic cells cross-prime cytotoxic T cells in vivo.
    J Exp Med. 2000 Dec 18;192(12):1685-96 PMID: 11120766
  58. Visualizing the generation of memory CD4 T cells in the whole body.
    Nature. 2001 Mar 1;410(6824):101-5 PMID: 11242050
  59. Preferential localization of effector memory cells in nonlymphoid tissue.
    Science. 2001 Mar 23;291(5512):2413-7 PMID: 11264538
  60. Migration and function of antigen-primed nonpolarized T lymphocytes in vivo.
    J Exp Med. 2001 Apr 16;193(8):987-93 PMID: 11304560
  61. Effector differentiation is not prerequisite for generation of memory cytotoxic T lymphocytes.
    J Clin Invest. 2001 Sep;108(6):871-8 PMID: 11560956
  62. Evidence for an accessory role of LFA-1 in lymphocyte-high endothelium interaction during homing.
    J Immunol. 1988 Feb 1;140(3):693-9 PMID: 3276776
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
Published
2001-10-01
Pages
953-66
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193483
Subset
IM
Grants
NHLBI NIH HHS · HL56949 · United States
NHLBI NIH HHS · HL48675 · United States
NHLBI NIH HHS · HL54936 · United States
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