CD4-CD8- T Cells Control Intracellular Bacterial Infections Both in Vitro and in Vivo

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2005 Jul 20

PMID 16027239

Citations 63

Authors

Siobhan C Cowley

Elizabeth Hamilton

Jeffrey A Frelinger

Jie Su

James Forman

Karen L Elkins

Affiliations

Soon will be listed here.

Abstract

Memory T cells, including the well-known CD4(+) and CD8(+) T cells, are central components of the acquired immune system and are the basis for successful vaccination. After infection, CD4(+) and CD8(+) T cells expand into effector cells, and then differentiate into long-lived memory cells. We show that a rare population of CD4(-)CD8(-)CD3(+)alphabeta(+)gammadelta(-)NK1.1(-) T cells has similar functions. These cells potently and specifically inhibit the growth of the intracellular bacteria Mycobacterium tuberculosis (M. tb.) or Francisella tularensis Live Vaccine Strain (LVS) in macrophages in vitro, promote survival of mice infected with these organisms in vivo, and adoptively transfer immunity to F. tularensis LVS. Furthermore, these cells expand in the spleens of mice infected with M. tb. or F. tularensis LVS, and then acquire a memory cell phenotype. Thus, CD4(-)CD8(-) T cells have a role in the control of intracellular infection and may contribute to successful vaccination.

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References

Kaech S, Wherry E, Ahmed R . Effector and memory T-cell differentiation: implications for vaccine development. Nat Rev Immunol. 2002; 2(4):251-62. DOI: 10.1038/nri778. View

Flynn J, Chan J . Immunology of tuberculosis. Annu Rev Immunol. 2001; 19:93-129. DOI: 10.1146/annurev.immunol.19.1.93. View

Ford M, Young K, Zhang Z, Ohashi P, Zhang L . The immune regulatory function of lymphoproliferative double negative T cells in vitro and in vivo. J Exp Med. 2002; 196(2):261-7. PMC: 2193928. DOI: 10.1084/jem.20020029. View

Johansson M, Lycke N . A unique population of extrathymically derived alpha beta TCR+CD4-CD8- T cells with regulatory functions dominates the mouse female genital tract. J Immunol. 2003; 170(4):1659-66. DOI: 10.4049/jimmunol.170.4.1659. View

Elkins K, Cowley S, Bosio C . Innate and adaptive immune responses to an intracellular bacterium, Francisella tularensis live vaccine strain. Microbes Infect. 2003; 5(2):135-42. DOI: 10.1016/s1286-4579(02)00084-9. View

Cowley S, Elkins K . Multiple T cell subsets control Francisella tularensis LVS intracellular growth without stimulation through macrophage interferon gamma receptors. J Exp Med. 2003; 198(3):379-89. PMC: 2194083. DOI: 10.1084/jem.20030687. View

Seder R, Ahmed R . Similarities and differences in CD4+ and CD8+ effector and memory T cell generation. Nat Immunol. 2003; 4(9):835-42. DOI: 10.1038/ni969. View

Blank C, Brown I, Marks R, Nishimura H, Honjo T, Gajewski T . Absence of programmed death receptor 1 alters thymic development and enhances generation of CD4/CD8 double-negative TCR-transgenic T cells. J Immunol. 2003; 171(9):4574-81. DOI: 10.4049/jimmunol.171.9.4574. View

Cowley S, Elkins K . CD4+ T cells mediate IFN-gamma-independent control of Mycobacterium tuberculosis infection both in vitro and in vivo. J Immunol. 2003; 171(9):4689-99. DOI: 10.4049/jimmunol.171.9.4689. View

10.

MacMicking J, Taylor G, McKinney J . Immune control of tuberculosis by IFN-gamma-inducible LRG-47. Science. 2003; 302(5645):654-9. DOI: 10.1126/science.1088063. View

11.

Kaech S, Tan J, Wherry E, Konieczny B, Surh C, Ahmed R . Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nat Immunol. 2003; 4(12):1191-8. DOI: 10.1038/ni1009. View

12.

Tyznik A, Sun J, Bevan M . The CD8 population in CD4-deficient mice is heavily contaminated with MHC class II-restricted T cells. J Exp Med. 2004; 199(4):559-65. PMC: 2211827. DOI: 10.1084/jem.20031961. View

13.

Carulli G, Lagomarsini G, Azzara A, Testi R, Riccioni R, Petrini M . Expansion of TcRalphabeta+CD3+CD4-CD8- (CD4/CD8 double-negative) T lymphocytes in a case of staphylococcal toxic shock syndrome. Acta Haematol. 2004; 111(3):163-7. DOI: 10.1159/000076526. View

14.

Sallusto F, Geginat J, Lanzavecchia A . Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol. 2004; 22:745-63. DOI: 10.1146/annurev.immunol.22.012703.104702. View

15.

Green L, Wagner D, Glogowski J, Skipper P, Wishnok J, Tannenbaum S . Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem. 1982; 126(1):131-8. DOI: 10.1016/0003-2697(82)90118-x. View

16.

Fortier A, Slayter M, Ziemba R, Meltzer M, Nacy C . Live vaccine strain of Francisella tularensis: infection and immunity in mice. Infect Immun. 1991; 59(9):2922-8. PMC: 258114. DOI: 10.1128/iai.59.9.2922-2928.1991. View

17.

Rahemtulla A, Schilham M, Kundig T, Sambhara S, Narendran A, Arabian A . Normal development and function of CD8+ cells but markedly decreased helper cell activity in mice lacking CD4. Nature. 1991; 353(6340):180-4. DOI: 10.1038/353180a0. View

18.

Cohen P, Eisenberg R . Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease. Annu Rev Immunol. 1991; 9:243-69. DOI: 10.1146/annurev.iy.09.040191.001331. View

19.

Dunn P, NORTH R . Resolution of primary murine listeriosis and acquired resistance to lethal secondary infection can be mediated predominantly by Thy-1+ CD4- CD8- cells. J Infect Dis. 1991; 164(5):869-77. DOI: 10.1093/infdis/164.5.869. View

20.

Elkins K, Nacy C, Winegar R, Fortier A . T-cell-independent resistance to infection and generation of immunity to Francisella tularensis. Infect Immun. 1993; 61(3):823-9. PMC: 302807. DOI: 10.1128/iai.61.3.823-829.1993. View