Roles of IFN-γ and γδ T cells in protective immunity against blood-stage malaria

Frontiers in Immunology

Volumn 4, Issue AUG, 2013, Pages

  Inoue, Shin Ichi ^a   Niikura, Mamoru ^a   Mineo, Shoichiro ^a   Kobayashi, Fumie ^a  

^a KYORIN UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

T cells; T cells; Dendritic cells; Hematopoiesis; IFN ; Malaria; Memory cells

Indexed keywords

B7 ANTIGEN; CD40 ANTIGEN; CD40 LIGAND; CD86 ANTIGEN; GAMMA INTERFERON; INTERLEUKIN 12; INTERLEUKIN 15; INTERLEUKIN 18; INTERLEUKIN 2; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; PERFORIN; PROGRAMMED DEATH 1 RECEPTOR; TOLL LIKE RECEPTOR;

ALPHA BETA T LYMPHOCYTE; ARTICLE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL ACTIVATION; CELL PROLIFERATION; DENDRITIC CELL; DISEASE SEVERITY; GAMMA DELTA T LYMPHOCYTE; HEMATOPOIESIS; HUMAN; IMMUNE RESPONSE; INNATE IMMUNITY; MACROPHAGE; MALARIA; MEMORY T LYMPHOCYTE; NATURAL KILLER CELL; NONHUMAN; PLASMODIUM; T LYMPHOCYTE;

EID: 84883712706     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2013.00258     Document Type: Article

References (94)

1. Amino R, Thiberge S, Martin B, Celli S, Shorte S, Frischknecht F, et al. Quantitative imaging of Plasmodium transmission from mosquito to mammal. Nat Med (2006) 12:220-4. doi:10.1038/nm1350
2. Artavanis-Tsakonas K, Riley EM. Innate immune response to malaria: rapid induction of IFN-γ from human NK cells by live Plasmodium falciparum-infected erythrocytes. J Immunol (2002) 169:2956-63.
3. Ing R, Stevenson MM. Dendritic cell and NK cell reciprocal cross talk promotes gamma interferon-dependent immunity to blood-stage Plasmodium chabaudi AS infection in mice. Infect Immun (2009) 77:770-82. doi:10.1128/IAI.00994-08
4. Roestenberg M, McCall M, Hopman J, Wiersma J, Luty AJ, van Gemert GJ, et al. Protection against a malaria challenge by sporozoite inoculation. N Engl J Med (2009) 361:468-77. doi:10.1056/NEJMoa0805832
5. Teirlinck AC, McCall MB, Roestenberg M, Scholzen A, Woestenenk R, de Mast Q, et al. Longevity and composition of cellular immune responses following experimental Plasmodium falciparum malaria infection in humans. PLoS Pathog (2011) 7:e1002389. doi:10.1371/journal.ppat.1002389
6. Flesch IE, Hess JH, Huang S, Aguet M, Rothe J, Bluethmann H, et al. Early interleukin 12 production by macrophages in response to mycobacterial infection depends on interferon γ and tumor necrosis factor a. J Exp Med (1995) 181:1615-21. doi:10.1084/jem.181.5.1615
7. Hilkens CM, Kalinski P, de Boer M, Kapsenberg ML. Human dendritic cells require exogenous interleukin-12-inducing factors to direct the development of naive T-helper cells toward the Th1 phenotype. Blood (1997) 90:1920-6.
8. Ohteki T, Fukao T, Suzue K, Maki C, Ito M, Nakamura M, et al. Interleukin 12-dependent interferon γ production by CD8a+ lymphoid dendritic cells. J Exp Med (1999) 189:1981-6. doi:10.1084/jem.189.12.1981
9. Suzue K, Asai T, Takeuchi T, Koyasu S. In vivo role of IFN-γ produced by antigen-presenting cells in early host defense against intracellular pathogens. Eur J Immunol (2003) 33:2666-75. doi:10.1002/eji.200323292
10. Moretto MM, Weiss LM, Combe CL, Khan IA. IFN-γ-producing dendritic cells are important for priming of gut intraepithelial lymphocyte response against intracellular parasitic infection. J Immunol (2007) 179:2485-92.
11. Buchmeier NA, Schreiber RD. Requirement of endogenous interferon-γ production for resolution of Listeria monocytogenes infection. Proc Natl Acad Sci U S A (1985) 82:7404-8. doi:10.1073/pnas.82.21.7404
12. Huang S, Hendriks W, Althage A, Hemmi S, Bluethmann H, Kamijo R, et al. Immune response in mice that lack the interferon-γ receptor. Science (1993) 259:1742-5. doi:10.1126/science.8456301
13. Kim BH, Shenoy AR, Kumar P, Das R, Tiwari S, MacMicking JD. A family of IFN-γ-inducible 65-kD GTPases protects against bacterial infection. Science (2011) 332:717-21. doi:10.1126/science.1201711
14. Green AM, Difazio R, Flynn JL. IFN-γ from CD4 T cells is essential for host survival and enhances CD8 T cell function during Mycobacterium tuberculosis infection. J Immunol (2013) 190:270-7. doi:10.4049/jimmunol.1200061
15. Murray HW, Rubin BY, Rothermel CD. Killing of intracellular Leishmania donovani by lymphokine-stimulated human mononuclear phagocytes. Evidence that interferon-? is the activating lymphokine. J Clin Invest (1983) 72:1506-10. doi:10.1172/JCI110972
16. Torrico F, Heremans H, Rivera MT, Van ME, Billiau A, Carlier Y. Endogenous IFN-γ is required for resistance to acute Trypanosoma cruzi infection in mice. J Immunol (1991) 146:3626-32.
17. Scharton-Kersten TM, Wynn TA, Denkers EY, Bala S, Grunvald E, Hieny S, et al. In the absence of endogenous IFN-γ, mice develop unimpaired IL-12 responses to Toxoplasma gondii while failing to control acute infection. J Immunol (1996) 157:4045-54.
18. Yamamoto M, Okuyama M, Ma JS, Kimura T, Kamiyama N, Saiga H, et al. A cluster of interferon-γ-inducible p65 GTPases plays a critical role in host defense against Toxoplasma gondii. Immunity (2012) 37:302-13. doi:10.1016/j.immuni.2012.06.009
19. Micallef MJ, Ohtsuki T, Kohno K, Tanabe F, Ushio S, Namba M, et al. Interferon-γ-inducing factor enhances T helper 1 cytokine production. Eur J Immunol (1996) 26:1647-51. doi:10.1002/eji.1830260736
20. Takeda K, Tsutsui H, Yoshimoto T, Adachi O, Yoshida N, Kishimoto T, et al. Defective NK cell activity and Th1 response in IL-18-deficient mice. Immunity (1998) 8:383-90. doi:10.1016/S1074-7613(00)80543-9
21. Okamoto I, Kohno K, Tanimoto T, Ikegami H, Kurimoto M. Development of CD8+ effector T cells is differentially regulated by IL-18 and IL-12. J Immunol (1999) 162:3202-11.
22. Kamath AT, Sheasby CE, Tough DF. Dendritic cells and NK cells stimulate bystander T cell activation in response to TLR agonists through secretion of IFN-aßand IFN-γ. J Immunol (2005) 174:767-76.
23. Munder M, Mallo M, Eichmann K, Modolell M. Murine macrophages secrete interferon-? upon combined stimulation with interleukin (IL)-12 and IL-18: a novel pathway of autocrine macrophage activation. J Exp Med (1998) 187:2103-8. doi:10.1084/jem.187.12.2103
24. Otani T, Nakamura S, Toki M, Motoda R, Kurimoto M, Orita K. Identification of IFN-γ-producing cells in IL-12/IL-18-treated mice. Cell Immunol (1999) 198:111-9. doi:10.1006/cimm.1999.1589
25. Fricke I, Mitchell D, Mittelstädt J, Lehan N, Heine H, Goldmann T, et al. Mycobacteria induce IFN-γ production in human dendritic cells via triggering of TLR2. J Immunol (2006) 176:5173-82.
26. Hiromatsu K, Yoshikai Y, Matsuzaki G, Ohga S, Muramori K, Matsumoto K, et al. A protective role of γd T cells in primary infection with Listeria monocytogenes in mice. J Exp Med (1992) 175:49-56. doi:10.1084/jem.175.1.49
27. Rosat JP, MacDonald HR, Louis JA. A role for γd T cells during experimental infection of mice with Leishmania major. J Immunol (1993) 150:550-5.
28. Hisaeda H, Nagasawa H, Maeda K, Maekawa Y, Ishikawa H, Ito Y, et al. γd T cells play an important role in hsp65 expression and in acquiring protective immune responses against infection with Toxoplasma gondii. J Immunol (1995) 155:244-51.
29. Wang T, Gao Y, Scully E, Davis CT, Anderson JF, Welte T, et al. γd T cells facilitate adaptive immunity against West Nile virus infection in mice. J Immunol (2006) 177:1825-32.
30. Déchanet J, Merville P, Lim A, Retière C, Pitard V, Lafarge X, et al. Implication of γd T cells in the human immune response to cytomegalovirus. J Clin Invest (1999) 103:1437-49. doi:10.1172/JCI5409
31. Egan CE, Dalton JE, Andrew EM, Smith JE, Gubbels MJ, Striepen B, et al. A requirement for the Vγ1+ subset of peripheral γd T cells in the control of the systemic growth of Toxoplasma gondii and infection-induced pathology. J Immunol (2005) 175:8191-9.
32. Inoue S, Niikura M, Takeo S, Mineo S, Kawakami Y, Uchida A, et al. Enhancement of dendritic cell activation via CD40 ligand-expressing γd T cells is responsible for protective immunity to Plasmodium parasites. Proc Natl Acad Sci U S A (2012) 109:12129-34. doi:10.1073/pnas.1204480109
33. Waki S, Uehara S, Kanbe K, Ono K, Suzuki M, Nariuchi H. The role of T cells in pathogenesis and protective immunity to murine malaria. Immunology (1992) 75:646-51.
34. Yoshimoto T, Takahama Y, Wang CR, Yoneto T, Waki S, Nariuchi H. A pathogenic role of IL-12 in blood-stage murine malaria lethal strain Plasmodium berghei NK65 infection. J Immunol (1998) 160:5500-5.
35. Yoneto T, Yoshimoto T, Wang CR, Takahama Y, Tsuji M, Waki S, et al. Gamma interferon production is critical for protective immunity to infection with blood-stage Plasmodium berghei XAT but neither NO production nor NK cell activation is critical. Infect Immun (1999) 67:2349-56.
36. Favre N, Ryffel B, Bordmann G, Rudin W. The course of Plasmodium chabaudi chabaudi infections in interferon-? receptor deficient mice. Parasite Immunol (1997) 19:375-83. doi:10.1046/j.1365-3024.1997.d01-227.x
37. van der Heyde HC, Pepper B, Batchelder J, Cigel F, Weidanz WP. The time course of selected malarial infections in cytokine-deficient mice. Exp Parasitol (1997) 85:206-13. doi:10.1006/expr.1996.4132
38. Amani V, Vigário AM, Belnoue E, Marussig M, Fonseca L, Mazier D, et al. Involvement of IFN-γ receptor-medicated signaling in pathology and anti-malarial immunity induced by Plasmodium berghei infection. Eur J Immunol (2000) 30:1646-55. doi:10.1002/1521-4141(200006)30:6<1646::AID-IMMU1646>3.0.CO;2-0
39. Su Z, Stevenson MM. Central role of endogenous γ interferon in protective immunity against blood-stage Plasmodium chabaudi AS infection. Infect Immun (2000) 68:4399-406. doi:10.1128/IAI.68.8.4399-4406.2000
40. Cigel F, Batchelder J, Burns JM Jr, Yañez D, van der Heyde H, Manning DD, et al. Immunity to blood-stage murine malarial parasites is MHC class II dependent. Immunol Lett (2003) 89:243-9. doi:10.1016/S0165-2478(03)00152-4
41. Süss G, Eichmann K, Kury E, Linke A, Langhorne J. Roles of CD4- and CD8-bearing T lymphocytes in the immune response to the erythrocytic stages of Plasmodium chabaudi. Infect Immunity (1988) 56:3081-8.
42. Podoba JE, Stevenson MM. CD4+ and CD8+ T lymphocytes both contribute to acquired immunity to blood-stage Plasmodium chabaudi AS. Infect Immun (1991) 59:51-8.
43. Imai T, Shen J, Chou B, Duan X, Tu L, Tetsutani K, et al. Involvement of CD8+ T cells in protective immunity against murine blood-stage infection with Plasmodium yoelii 17XL strain. Eur J Immunol (2010) 40:1053-61. doi:10.1002/eji.200939525
44. Butler NS, Moebius J, Pewe LL, Traore B, Doumbo OK, Tygrett LT, et al. Therapeutic blockade of PD-L1 and LAG-3 rapidly clears established blood-stage Plasmodium infection. Nat Immunol (2011) 13(2):188-95. doi:10.1038/ni.2180
45. Coban C, Ishii KJ, Kawai T, Hemmi H, Sato S, Uematsu S, et al. Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin. J Exp Med (2005) 201:19-25. doi:10.1084/jem.20041836
46. Parroche P, Lauw FN, Goutagny N, Latz E, Monks BG, Visintin A, et al. Malaria hemozoin is immunologically inert but radically enhances innate responses by presenting malaria DNA to Toll-like receptor 9. Proc Natl Acad Sci U S A (2007) 104:1919-24. doi:10.1073/pnas.0608745104
47. Seixas E, Moura Nunes JF, Matos I, Coutinho A. The interaction between DC and Plasmodium berghei/chabaudi-infected erythrocytes in mice involves direct cell-to-cell contact, internalization and TLR. Eur J Immunol (2009) 39:1850-63. doi:10.1002/eji.200838403
48. Gowda NM, Wu X, Gowda DC. TLR9 and MyD88 are crucial for the development of protective immunity to malaria. J Immunol (2012) 188:5073-85. doi:10.4049/jimmunol.1102143
49. Morita CT, Beckman EM, Bukowski JF, Tanaka Y, Band H, Bloom BR, et al. Direct presentation of nonpeptide prenyl pyrophosphate antigens to human γd T cells. Immunity (1995) 3:495-507. doi:10.1016/1074-7613(95)90178-7
50. Behr C, Poupot R, Peyrat MA, Poquet Y, Constant P, Dubois P, et al. Plasmodium falciparum stimuli for human γd T cells are related to phosphorylated antigens of mycobacteria. Infect Immun (1996) 64:2892-6.
51. Pichyangkul S, Saengkrai P, Yongvanitchit K, Stewart A, Heppner DG. Activation of γd T cells in malaria: interaction of cytokines and a schizont-associated Plasmodium falciparum antigen. J Infect Dis (1997) 176:233-41. doi:10.1086/514029
52. Elloso MM, Van der Heyde HC, Troutt A, Manning DD, Weidanz WP. Human γd T cell subset-proliferative response to malarial antigen in vitro depends on CD4+ T cells or cytokines that signal through components of the IL-2R. J Immunol (1996) 157:2096-102.
53. Ribot JC, Debarros A, Mancio-Silva L, Pamplona A, Silva-Santos B. B7-CD28 costimulatory signals control the survival and proliferation of murine and human γd T cells via IL-2 production. J Immunol (2012) 189:1202-8. doi:10.4049/jimmunol.1200268
54. Mokuno Y, Matsuguchi T, Takano M, Nishimura H, Washizu J, Ogawa T, et al. Expression of toll-like receptor 2 on γd T cells bearing invariant Vγ6/Vd1 induced by Escherichia coli infection in mice. J Immunol (2000) 165:931-40.
55. Deetz CO, Hebbeler AM, Propp NA, Cairo C, Tikhonov I, Pauza CD. Gamma interferon secretion by human Vγ2Vd2 T cells after stimulation with antibody against the T-cell receptor plus the toll-like receptor 2 agonist Pam3Cys. Infect Immun (2006) 74:4505-11. doi:10.1128/IAI.00088-06
56. Pietschmann K, Beetz S, Welte S, Martens I, Gruen J, Oberg HH, et al. Toll-like receptor expression and function in subsets of human γd T lymphocytes. Scand J Immunol (2009) 70:245-55. doi:10.1111/j.1365-3083.2009.02290.x
57. Naik RS, Branch OH, Woods AS, Vijaykumar M, Perkins DJ, Nahlen BL, et al. Glycosylphosphatidylinositol anchors of Plasmodium falciparum: molecular characterization and naturally elicited antibody response that may provide immunity to malaria pathogenesis. J Exp Med (2000) 192:1563-76. doi:10.1084/jem.192.11.1563
58. Devilder MC, Allain S, Dousset C, Bonneville M, Scotet E. Early triggering of exclusive IFN-γ responses of human Vγ9Vd2 T cells by TLR-activated myeloid and plasmacytoid dendritic cells. J Immunol (2009) 183:3625-33. doi:10.4049/jimmunol.0901571
59. D'Ombrain MC, Robinson LJ, Stanisic DI, Taraika J, Bernard N, Michon P, et al. Association of early interferon-gamma production with immunity to clinical malaria: a longitudinal study among Papua New Guinean children. Clin Infect Dis (2008) 47:1380-7. doi:10.1086/592971
60. Belnoue E, Kayibanda M, Vigario AM, Deschemin JC, van Rooijen N, Viguier M, et al. On the pathogenic role of brain-sequestered aßCD8+ T cells in experimental cerebral malaria. J Immunol (2002) 169:6369-75.
61. Villegas-Mendez A, Greig R, Shaw TN, de Souza JB, Gwyer Findlay E, Stumhofer JS, et al. IFN-γ-producing CD4+ T cells promote experimental cerebral malaria by modulating CD8+ T cell accumulation within the brain. J Immunol (2012) 189:968-79. doi:10.4049/jimmunol.1200688
62. Yañez DM, Manning DD, Cooley AJ, Weidanz WP, van der Heyde HC. Participation of lymphocyte subpopulations in the pathogenesis of experimental murine cerebral malaria. J Immunol (1996) 157:1620-4.
63. Nitcheu J, Bonduelle O, Combadiere C, Tefit M, Seilhean D, Mazier D, et al. Perforin-dependent brain-infiltrating cytotoxic CD8+ T lymphocytes mediate experimental cerebral malaria pathogenesis. J Immunol (2003) 170:2221-8.
64. Haque A, Best SE, Unosson K, Amante FH, de Labastida F, Anstey NM, et al. Granzyme B expression by CD8+ T cells is required for the development of experimental cerebral malaria. J Immunol (2011) 186:6148-56. doi:10.4049/jimmunol.1003955
65. Lundie RJ, de Koning-Ward TF, Davey GM, Nie CQ, Hansen DS, Lau LS, et al. Blood-stage Plasmodium infection induces CD8+ T lymphocytes to parasite-expressed antigens, largely regulated by CD8a+ dendritic cells. Proc Natl Acad Sci U S A (2008) 105:14509-14. doi:10.1073/pnas.0806727105
66. Yañez DM, Batchelder J, van der Heyde HC, Manning DD, Weidanz WP. γd T-cell function in pathogenesis of cerebral malaria in mice infected with Plasmodium berghei ANKA. Infect Immun (1999) 67:446-8.
67. Baldridge MT, King KY, Boles NC, Weksberg DC, Goodell MA. Quiescent haematopoietic stem cells are activated by IFN-γ in response to chronic infection. Nature (2010) 465:793-7. doi:10.1038/nature09135
68. Katherine C, MacNamara KC, Oduro K, Martin O, Jones DD, McLaughlin M, et al. Infection-induced myelopoiesis during intracellular bacterial infection is critically dependent upon IFN-γ signaling. J Immunol (2011) 186:1032-43. doi:10.4049/jimmunol.1001893
69. MacNamara KC, Jones M, Martin O, Winslow GM. Transient activation of hematopoietic stem and progenitor cells by IFNγ during acute bacterial infection. PLoS ONE (2011) 6:e28669. doi:10.1371/journal.pone.0028669
70. Belyaev NN, Brown DE, Diaz AI, Rae A, Jarra W, Thompson J, et al. Induction of an IL7-R+c-Kithi myelolymphoid progenitor critically dependent on IFN-γ signaling during acute malaria. Nat Immunol (2010) 11:477-85. doi:10.1038/ni.1869
71. Sato T, Selleri C, Young NS, MacIejewski JP. Hematopoietic inhibition by interferon-γ is partially mediated through interferon regulatory factor-1. Blood (1995) 86:3373-80.
72. de Bruin AM, Buitenhuis M, van der Sluijs KF, van Gisbergen KP, Boon L, Nolte MA. Eosinophil differentiation in the bone marrow is inhibited by T cell-derived IFN-γ. Blood (2010) 116:2559-69. doi:10.1182/blood-2009-12-261339
73. Libregts SF, Gutiérrez L, de Bruin AM, Wensveen FM, Papadopoulos P, van Ijcken W, et al. Chronic IFN-γ production in mice induces anemia by reducing erythrocyte life span and inhibiting erythropoiesis through an IRF-1/PU.1 axis. Blood (2011) 118:2578-88. doi:10.1182/blood-2010-10-315218
74. Falini B, Flenghi L, Pileri S, Pelicci P, Fagioli M, Martelli MF, et al. Distribution of T cells bearing different forms of the T cell receptor gamma/delta in normal and pathological human tissues. J Immunol (1989) 143:2480-8.
75. van der Heyde HC, Elloso MM, Chang WL, Kaplan M, Manning DD, Weidanz WP. γd T cells function in cell-mediated immunity to acute blood-stage Plasmodium chabaudi adami malaria. J Immunol (1995) 154:3985-90.
76. Seixas EM, Langhorne J. γd T cells contribute to control of chronic parasitemia in Plasmodium chabaudi infections in mice. J Immunol (1999) 162:2837-41.
77. Bakir HY, Tomiyama-Miyaji C, Watanabe H, Nagura T, Kawamura T, Sekikawa H, et al. Reasons why DBA/2 mice are resistant to malaria infection; expansion of CD3int B220+ γd T cells with double-negative CD4-CD8-phenotype in the liver. Immunology (2006) 117:127-35. doi:10.1111/j.1365-2567.2005.02273.x
78. Weidanz WP, LaFleur G, Brown A, Burns JM Jr, Gramaglia I, van der Heyde HC. γd T cells but not NK cells are essential for cell-mediated immunity against Plasmodium chabaudi malaria. Infect Immun (2010) 78:4331-40. doi:10.1128/IAI.00539-10
79. Costa G, Loizon S, Guenot M, Mocan I, Halary F, de Saint-Basile G, et al. Control of Plasmodium falciparum erythrocytic cycle: γd T cells target the red blood cell-invasive merozoites. Blood (2011) 118:6952-62. doi:10.1182/blood-2011-08-376111
80. Kobayashi F, Niikura M, Waki S, Matsui T, Fujino T, Tsuruhara T, et al. Plasmodium berghei XAT: contribution of γd T cells to host defense against infection with blood-stage nonlethal malaria parasite. Exp Parasitol (2007) 117:368-75. doi:10.1016/j.exppara.2007.05.002
81. Waki S, Tamura J, Imanaka M, Ishikawa S, Suzuki M. Plasmodium berghei: isolation and maintenance of an irradiation attenuated strain in the nude mouse. Exp Parasitol (1982) 53:335-40. doi:10.1016/0014-4894(82)90076-5
82. Nakazawa S, Brown AE, Maeno Y, Smith CD, Aikawa M. Malaria-induced increase of splenic γd T cells in humans, monkeys, and mice. Exp Parasitol (1994) 79:391-8. doi:10.1006/expr.1994.1101
83. Horowitz A, Newman KC, Evans JH, Korbel DS, Davis DM, Riley EM. Cross-talk between T cells and NK cells generates rapid effector responses to Plasmodium falciparum-infected erythrocytes. J Immunol (2010) 184:6043-52. doi:10.4049/jimmunol.1000106
84. Hudspeth K, Fogli M, Correia DV, Mikulak J, Roberto A, Della Bella S, et al. Engagement of NKp30 on Vd1 T cells induces the production of CCL3, CCL4, and CCL5 and suppresses HIV-1 replication. Blood (2012) 119:4013-6. doi:10.1182/blood-2011-11-390153
85. Vermijlen D, Ellis P, Langford C, Klein A, Engel R, Willimann K, et al. Distinct cytokine-driven responses of activated blood γd T cells: insights into unconventional T cell pleiotropy. J Immunol (2007) 178:4304-14.
86. Schulz O, Edwards AD, Schito M, Aliberti J, Manickasingham S, Sher A, et al. CD40 triggering of heterodimeric IL-12 p70 production by dendritic cells in vivo requires a microbial priming signal. Immunity (2000) 13:453-62. doi:10.1016/S1074-7613(00)00045-5
87. Kaech SM, Wherry EJ, Ahmed R. Effector and memory T-cell differentiation: implications for vaccine development. Nat Rev Immunol (2002) 2:251-62. doi:10.1038/nri778
88. Kalia V, Sarkar S, Gourley TS, Rouse BT, Ahmed R. Differentiation of memory B and T cells. Curr Opin Immunol (2006) 18:255-64. doi:10.1016/j.coi.2006.03.020
89. Freitas do Rosário AP, Muxel SM, Rodríguez-Málaga SM, Sardinha LR, Zago CA, Castillo-Méndez SI, et al. Gradual decline in malaria-specific memory T cell responses leads to failure to maintain long-term protective immunity to Plasmodium chabaudi AS despite persistence of B cell memory and circulating antibody. J Immunol (2008) 181:8344-55.
90. Stephens R, Langhorne J. Effector memory Th1 CD4 T cells are maintained in a mouse model of chronic malaria. PLoS Pathog (2010) 6:e1001208. doi:10.1371/journal.ppat.1001208
91. Shen Y, Zhou D, Qiu L, Lai X, Simon M, Shen L, et al. Adaptive immune response of Vγ2Vd2 T cells during mycobacterial infections. Science (2002) 295:2255-8. doi:10.1126/science.1068819
92. Pitard V, Roumanes D, Lafarge X, Couzi L, Garrigue I, Lafon ME, et al. Long-term expansion of effector/memory Vd2-γd T cells is a specific blood signature of CMV infection. Blood (2008) 112:1317-24. doi:10.1182/blood-2008-01-136713
93. Tokoyoda K, Zehentmeier S, Hegazy AN, Albrecht I, Grün JR, Löhning M, et al. Professional memory CD4+ T lymphocytes preferentially reside and rest in the bone marrow. Immunity (2009) 30:721-30. doi:10.1016/j.immuni.2009.03.015
94. Rudin W, Favre N, Bordmann G, Ryffel B. Interferon-γ is essential for the development of cerebral malaria. Eur J Immunol (1997) 27:810-5. doi:10.1002/eji.1830270403