The immunology of susceptibility and resistance to Leishmania major in mice

Nature Reviews Immunology

Volumn 2, Issue 11, 2002, Pages 845-858

  Sacks, David ^a   Noben Trauth, Nancy ^b  

^a NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^b GEORGE WASHINGTON UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; CYTOKINE; GAMMA INTERFERON; GREEN FLUORESCENT PROTEIN; INTERLEUKIN 12; INTERLEUKIN 4; LEISHMANIA VACCINE; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; PLASMID DNA; RECOMBINANT PROTEIN; T LYMPHOCYTE RECEPTOR; PROTOZOAL VACCINE;

ANIMAL MODEL; CELLULAR IMMUNITY; DISEASE PREDISPOSITION; DISEASE RESISTANCE; IMMUNE RESPONSE; IMMUNOBIOLOGY; LEISHMANIA MAJOR; LEISHMANIASIS; LIFE CYCLE; MOUSE; NONHUMAN; PRIORITY JOURNAL; REVIEW; SCID MOUSE; ANIMAL; BAGG ALBINO MOUSE; CD8+ T LYMPHOCYTE; HUMAN; IMMUNOLOGY; PHYSIOLOGY; SKIN LEISHMANIASIS; TH1 CELL; TH2 CELL;

ANIMALS; CD8-POSITIVE T-LYMPHOCYTES; DISEASE SUSCEPTIBILITY; HUMANS; INTERLEUKIN-12; INTERLEUKIN-4; LEISHMANIA MAJOR; LEISHMANIASIS, CUTANEOUS; MICE; MICE, INBRED BALB C; PROTOZOAN VACCINES; TH1 CELLS; TH2 CELLS;

EID: 0036831673     PISSN: 14741733     EISSN: None     Source Type: Journal    
DOI: 10.1038/nri933     Document Type: Review

References (140)

1. Sadick, M. D. et al. Cure of murine leishmaniasis with anti-interleukin-4 monoclonal antibody. Evidence for a T-cell-dependent, interferon-γ-independent mechanism. J. Exp. Med, 171, 115-127 (1990).
2. H2 response in Leishmania major-infected mice. J. Immunol. 148, 1182-1187 (1992).
3. Kopf, M. et al. IL-4-deficient BALB/c mice resist infection with Leishmania major. J. Exp. Med. 184, 1127-1136 (1996).
4. Mohrs, M. et al. Differences between IL-4- and IL-4 receptor α-deficient mice in chronic leishmaniasis reveal a protective role for IL-13 receptor signaling. J. Immunol. 162, 7302-7308 (1999). References 1-4 provide strong evidence that the production of IL-4 is essential for susceptibility to Leishmania major.
5. H2 development and susceptibility to Leishmania major in BALB/c mice. Immunity 6, 541-549 (1997).
6. H2-cell development resulting in progressive disease. J. Immunol. 164, 4819-4825 (2000).
7. Julia, V., Rassoulzadegan, M. & Glaichenhaus, N, Resistance to Leishmania major induced by tolerance to a single antigen. Science 274, 421-423 (1996). References 5-7 make the strong case that early IL-4 production by LACK-reactive cells controls susceptibility to L. major.
8. + T cells in resistant mice upon infection with Leishmania major. Immunity 13, 771-782 (2000).
9. Shankar, A. H. & Titus, R. G. T-cell and non-T-cell compartments can independently determine resistance to Leishmania major. J. Exp. Med. 181, 845-855 (1995).
10. H2 cell antigen receptors in experimental leishmaniasis. Science 259, 1457-1460 (1993).
11. + T cells which react to the Leishmania major LACK antigen rapidly secrete interleukin-4 and are detrimental to the host in resistant B10.D2 mice Infect. Immun. 67, 3641-3644 (1999).
12. Stetson, D. B., Mohrs, M., Mattlet-Designe, V., Teyton, L. & Locksley, R. M. Rapid expansion and IL-4 expression by Leishmania-specific naive helper T cells in vivo. Immunity 17, 191-200 (2002). A convincing demonstration that early IL-4 production by LACK-reactive cells occurs in both susceptible and resistant mouse strains.
13. + cells correlate with resolution of lesions in murine cutaneous leishmaniasis. J. Immunol. 149, 2715-2721 (1992).
14. Belkaid, Y. et al. A natural model of Leishmania major infection reveals a prolonged 'silent' phase of parasite amplification in the skin before the onset of lesion formation and immunity. J. Immunol. 165, 969-977 (2000).
15. + T cells during initiation of infection J. Exp. Med. 179, 447-456 (1994). A thorough demonstration that L. major promastigotes behave as 'stealth' parasites in infected macrophages.
16. Scott, P., Eaton, A., Gause, W. C., di Zhou, X. & Hondowicz, B. Early IL-4 production does not predict susceptibility to Leishmania major. Exp. Parasitol. 84, 178-187 (1996). Early evidence that a rapid IL-4 response occurs in resistant, as well as susceptible, mice.
17. H2 cytokine responses capable of exacerbating leishmaniasis in normally resistant mice. J. Immunol. 155, 730-739 (1995).
18. H2 response. J. Immunol. 159, 5024-5031 (1997).
19. H1 immune response. Immunol. Cell. Biol. 74, 239-244 (1996).
20. Leal, L. M., Moss, D. W., Kuhn, R., Muller, W. & Liew, F. Y. Interleukin-4-transgenic mice of resistant background are susceptible to Leishmania major infection. Eur. J. Immunol. 23, 566-569 (1993).
21. Groux, H. et al. A transgenic model to analyze the immunoregulatory role of IL-10 secreted by antigen-presenting cells. J. Immunol. 162, 1723-1729 (1999).
22. + T cells that are a subset of an immunoregulatory population that can suppress colitis also.
23. Bogdan, C., Rollinghoff, M. & Diefenbach, A. Reactive oxygen and reactive nitrogen intermediates in innate and specific immunity. Curr. Opin. Immunol. 12, 64-76 (2000).
24. Heinzel, F. P., Schoenhaut, D. S., Rerko, R. M., Rosser, L. E. & Gately, M. K. Recombinant interleukin-12 cures mice infected with Leishmania major. J. Exp. Med. 177, 1505-1509 (1993).
25. H1 response and resistance to L. major.
26. H2 cell response. Eur. J. Immunol. 26, 1553-1559 (1996).
27. H2 response in Leishmania major-infected mice. Eur. J. Immunol. 30, 2007-2014 (2000).
28. + T cells resulting in a state of unresponsiveness to IL-12. J. Immunol. 161, 6156-6163 (1998).
29. H1 cell development. Science 271, 984-987 (1996).
30. Nishikomori, R., Gurunathan, S., Nishikomori, K. & Strober, W. BALB/ c mice bearing a transgenic IL-12 receptor-β2 gene exhibit a nonhealing phenotype to Leishmania major infection despite intact IL-12 signaling. J. Immunol. 166, 6776-6783 (2001).
31. Beil, W. J., Meinardus-Hager, G., Neugebauer, D. C. & Sorg, C. Differences in the onset of the inflammatory response to cutaneous leishmaniasis in resistant and susceptible mice. J. Leukocyte Biol. 52, 135-142 (1992).
32. H2 response in BALB/c mice infected with Leishmania major. J. Immunol. 165, 2628-2636 (2000).
33. Laskay, T., Diefenbach, A., Rollinghoff, M. & Solbach, W. Early parasite containment is decisive for resistance to Leishmania major infection. Eur. J. Immunol. 25, 2220-2227 (1995). The first demonstration that L. major promastigotes disseminate rapidly to the viscera in BALB/c mice, but not in resistant mice.
34. + T cells in the liver spontaneously produce IL-4 in vitro during the early phase of Leishmania major infection in susceptible BALB/c mice. Acta Trop. 73, 109-119 (1999).
35. H2-type immune responses in (BALB/c × C57BL/6) F1 mice infected with Leishmania major. Parasite Immunol. 17, 569-579 (1995).
36. H2-type differentiation. Eur. J. Immunol. 30, 840-847 (2000). A clear demonstration that the tissue site of parasite delivery can influence the class of effector cell that is induced.
37. H2-like cytokine responses in vitro and in vivo J. Immunol. 164, 1346-1354 (2000).
38. H2 polarization by the chemokine monocyte chemoattractant protein-1. Nature 404, 407-411 (2000).
39. H-subset response and alters the course of experimental Leishmania major infection. Eur. J. Immunol. 28, 4213-4220 (1998).
40. H2 effector cells in experimental leishmaniasis. J. Immunol. 153, 4142-4148 (1994).
41. H2 response. J. Infect. Dis. 174, 1303-1308 (1996).
42. Akiba, H. et al. Critical contribution of OX40 ligand to T helper cell type 2 differentiation in experimental leishmaniasis. J. Exp. Med. 191, 375-380 (2000).
43. von Stebut, E. et al. Leishmania major-infected murine Langerhans cell-like dendritic cells from susceptible mice release IL-12 after infection and vaccinate against experimental cutaneous Leishmaniasis. Eur. J. Immunol. 30, 3498-3506 (2000).
44. Bretscher, P. A., Wei, G., Menon, J. N. & Bielefeldt-Ohmann, H. Establishment of stable, cell-mediated immunity that makes 'susceptible' mice resistant to Leishmania major. Science 257, 539-542 (1992). Strong evidence that parasite dose can influence the effector class.
45. Howard, J. G., Nicklin, S., Hale, C. & Liew, F. Y. Prophylactic immunization against experimental leishmaniasis. I. Protection induced in mice genetically vulnerable to fatal Leishmania tropica infection. J. Immunol. 129, 2206-2212 (1982).
46. Aebischer, T., Morris, L. & Handman, E. Intravenous injection of irradiated Leishmania major into susceptible BALB/c mice: immunization or protective tolerance. Int. Immunol. 6, 1535-1543 (1994).
47. Beebe, A. M., Mauze, S., Schork, N. J. & Coffman, R. L. Serial backeross mapping of multiple loci associated with resistance to Leishmania major in mice. Immunity 6, 551-557 (1997).
48. Lipoldova, M. et al. Susceptibility to Leishmania major infection in mice: multiple loci and heterogeneity of immunopathological phenotypes. Genes Immun. 1, 200-206 (2000).
49. Noben-Trauth, N., Paul, W. E. & Sacks, D. L. IL-4- and IL-4-receptor-deficient BALB/c mice reveal differences in susceptibility to Leishmania major parasite substrains. J. Immunol. 162, 6132-6140 (1999).
50. Matthews, D. J. et al. IL-13 is a susceptibility factor for Leishmania major infection. J. Immunol. 164, 1458-1462 (2000).
51. Noben-Trauth, N., Kropf, P. & Muller, I. Susceptibility to Leishmania major infection in interleukin-4-deficient mice. Science 271, 987-990 (1996). The first serious challenge to the established model regarding the role of IL-4 in susceptibility to L. major.
52. H2 marker ST2L in the absence of IL-4 during Leishmania major infection. Eur. J. Immunol. 29, 3621-3628 (1999).
53. Li, J. J., Hunter, C. A. & Farrell, J. P. Anti-TGF-β treatment promotes rapid healing of Leishmania major infection in mice by enhancing in vivo nitric oxide production. J. Immunol. 162, 974-979 (1999).
54. Gorelik, L., Constant, S. L. & Flavell, R. A. Mechanism of transforming growth factor-β-induced inhibition of T helper type I differentiation. J. Exp. Med. 195, 1499-1505 (2002).
55. Chatelain, R., Mauze, S. & Coffman, R. L. Experimental Leishmania major infection in mice: role of IL-10. Parasite Immunol. 21, 211-218 (1999).
56. Yamakami, K. et al. Administration of plasmids expressing interleukin-4 and interleukin-10 causes BALB/c mice to induce a T helper 2-type response, despite the expected T helper 1-type response, with a low-dose infection of Leishmania major. Immunology 105, 515-523 (2002).
57. Kane, M. M. & Mosser D. M. The role of IL-10 in promoting disease progression in leishmaniasis. J. Immunol. 166, 1141-1147 (2001). A clear demonstration that IL-10 contributes to susceptibility to L. major in BALB/c mice.
58. Kropf, P. et al. Characterization of T-cell-mediated responses in nonhealing and healing Leishmania major infections in the absence of endogenous IL-4. J. Immunol. 159, 3434-3443 (1997).
59. + suppressor T cells. J. Exp. Med. 193, F41-F46 (2001).
60. Mohrs, M., Holscher, C. & Brombacher, F. Interleukin-4 receptor α-deficient BALB/c mice show an unimpaired T helper 2 polarization in response to Leishmania major infection. Infect. Immun. 68, 1773-1780 (2000).
61. Melby, P. C. et al. Increased expression of proinflammatory cytokines in chronic lesions of human cutaneous leishmaniasis. Infect. Immun. 62, 837-842 (1994).
62. Karp, C. L. et al. In vivo cytokine profiles in patients with kala-azar. Marked elevation of both interleukin-10 and interferon-γ. J. Clin. Invest. 91, 1644-1648 (1993).
63. Gasim, S. et al. High levels of plasma IL-10 and expression of IL-10 by keratinocytes during visceral leishmaniasis predict subsequent development of post-kala-azar dermal leishmaniasis. Clin. Exp. Immunol. 111, 64-69 (1998).
64. H2 pathway in interferon-γ-deficient mice infected with Leishmania major. J. Exp. Med. 179, 1367-1371 (1994).
65. H1 lineage commitment and IFN-γ production in CD4 and CD8 T cells. Science 295, 338-342 (2002).
66. Campbell, K. A. et al. CD40 ligand is required for protective cell-mediated immunity to Leishmania major. Immunity 4, 283-289 (1996).
67. Kamanaka, M. et al. Protective role of CD40 in Leishmania major infection at two distinct phases of cell-mediated immunity. Immunity 4, 275-281 (1996).
68. + T-cell response. J. Exp. Med. 181, 961-971 (1995).
69. Stamm, L. M., Satoskar, A. A., Ghosh, S. K., David, J. R. & Satoskar, A. R. STAT-4-mediated IL-12 signaling pathway is critical for the development of protective immunity in cutaneous leishmaniasis. Eur. J. Immunol. 29, 2524-2529 (1999).
70. H1 response and control cutaneous Leishmania major infection. J. Immunol. 164, 5890-5893 (2000).
71. Wei, X. et al. Altered immune responses and susceptibility to Leishmania major and Staphylococcus aureus infection in IL-18-deficient mice. J. Immunol. 163, 2821-2828 (1999).
72. H1 responses and resistance to L. major infection. Immunity 15, 569-578 (2001).
73. H1 response during Leishmania major infection. J. Immunol. 165, 896-902 (2000).
74. H1 effector cells.
75. Park, A. Y. & Scott, P. IL-12: keeping cell-mediated immunity alive. Scand. J. Immunol. 53, 529-532 (2001).
76. Carrera, L. et al. Leishmania promastigotes selectively inhibit interleukin-12 induction in bone-marrow-derived macrophages from susceptible and resistant mice. J. Exp. Med. 183, 515-526 (1996).
77. Sartori, A., Oliveira, M. A., Scott, P. & Trinchieri, G. Metacyclogenesis modulates the ability of Leishmania promastigotes to induce IL-12 production in human mononuclear cells. J. Immunol. 159, 2849-2857 (1997).
78. Blank, C., Fuchs, H., Rappersberger, K., Rollinghoff, M. & Moll, H. Parasitism of epidermal Langerhans cells in experimental cutaneous leishmaniasis with Leishmania major. J. Infect. Dis. 167, 418-425 (1993).
79. von Stebut, E., Belkaid, Y., Jakob, T., Sacks, D. L. & Udey, M. C. Uptake of Leishmania major amastigotes results in activation and interleukin-12 release from murine skin-derived dendritic cells: implications for the initiation of anti-Leishmania immunity. J. Exp. Med. 188, 1547-1552 (1998).
80. Konecny, P. et al. Murine dendritic cells internalize Leishmania major promastigotes, produce IL-12 p40 and stimulate primary T-cell proliferation in vitro. Eur. J. Immunol. 29, 1803-1811 (1999).
81. Moll, H. & Flohe, S. Dendritic cells induce immunity to cutaneous leishmaniasis in mice. Adv. Exp. Med. Biol. 417, 541-545 (1997).
82. Moll, H., Fuchs, H., Blank, C. & Rollinghoff, M. Langerhans cells transport Leishmania major from the infected skin to the draining lymph node for presentation to antigen-specific T cells. Eur. J. Immunol. 23, 1595-1601 (1993). Part of an early series of papers from this group showing the role of dendritic cells in T-cell priming.
83. H2 cytokines, B-cell outgrowth and sustained neutrophilic inflammation. J. Exp. Med. 192, 205-218 (2000).
84. + T-cell subsets and induces early resistance to Leishmania major in mice. J. Exp. Med. 178, 567-577 (1993).
85. + T cells is sufficient to mediate T helper cell type 1 development. J. Exp. Med. 188, 1651-1656 (1998).
86. H1 response and control cutaneous Leishmania major infection. J. Immunol. 162, 6747-6754 (1999).
87. Bogdan, C., Moll, H., Solbach, W. & Rollinghoff, M. Tumor necrosis factor-α in combination with interferon-γ, but not with interleukin-4, activates murine macrophages for elimination of Leishmania major amastigotes. Eur. J. Immunol. 20, 1131-1135 (1990).
88. Wei, X. Q. et al. Altered immune responses in mice lacking inducible nitric oxide synthase. Nature 375, 408-411 (1995).
89. Wilhelm, P. et al. Rapidly fatal leishmaniasis in resistant C57BL/6 mice lacking TNF. J. Immunol. 166, 4012-4019 (2001).
90. Nashleanas, M., Kanaly, S. & Scott, P. Control of Leishmania major infection in mice lacking TNF receptors. J. Immunol. 160, 5506-5513 (1998).
91. H1 responses and enhanced nitric oxide production J. Immunol. 160, 4143-4147 (1998).
92. Conceicao-Silva, F., Hahne, M., Schroter, M., Louis, J. & Tschopp, J. The resolution of lesions induced by Leishmania major in mice requires a functional Fas (APO-1, CD95) pathway of cytotoxicity. Eur. J. Immunol. 28, 237-245 (1998).
93. Chakkalath, H. R. et al. Class II major histocompatibility complex-deficient mice initially control an infection with Leishmania major but succumb to the disease. J. Infect. Dis. 171, 1302-1308 (1995).
94. + T cells do not mediate a protective immune response. Immunobiology 195, 243-260 (1996).
95. Muller, I. Role of T-cell subsets during the recall of immunologic memory to Leishmania major. Eur. J. Immunol. 22, 3063-3069 (1992).
96. Huber, M., Timms, E., Mak, T. W., Rollinghoff, M. & Lohoff, M. Effective and long-lasting immunity against the parasite Leishmania major in CD8-deficient mice. Infect. Immun. 66, 3968-3970 (1998).
97. + T cells in the immunological control of experimentally induced murine cutaneous leishmaniasis. Eur. J. Immunol. 17, 1429-1433 (1987).
98. + T cells are essential for primary immunity in resistant mice.
99. + T cells associated with cure of human cutaneous leishmaniasis. Infect. Immun, 62, 2614-2618 (1994).
100. Gaafar, A. et al. Characterization of the local and systemic immune responses in patients with cutaneous leishmaniasis due to Leishmania major. Clin. Immunol. 91, 314-320 (1999).
101. Bogdan, C. et al. Fibroblasts as host cells in latent leishmaniasis. J. Exp. Med. 191, 2121-2130 (2000).
102. Moll, H., Flohe, S. & Blank, C. Dendritic cells seclude Leishmania parasites that persist in cured mice - a role in the maintenance of T-cell memory? Adv. Exp. Med Biol. 378, 507-509 (1995).
103. Aebischer, T., Moody, S. F. & Handman, E. Persistence of virulent Leishmania major in murine cutaneous leishmaniasis: a possible hazard for the host. Infect. Immun. 61, 220-226 (1993). One of the first demonstrations that L. major persists after healing in resistant mice.
104. Stenger, S., Donhauser, N., Thuring, H., Rollinghoff, M. & Bogdan, C. Reactivation of latent leishmaniasis by inhibition of inducible nitric oxide synthase. J. Exp. Med. 183, 1501-1514 (1996).
105. Belkaid, Y. et al. The role of interleukin (IL)-10 in the persistence of Leishmania major in the skin after healing and the therapeutic potential of anti-IL-10 receptor antibody for sterile cure. J. Exp. Med. 194, 1497-1506 (2001). A demonstration that IL-10 is required for L. major persistence in healed mice.
106. Louzir, H. et al. Immunologic determinants of disease evolution in localized cutaneous leishmaniasis due to Leishmania major. J. Infect. Dis. 177, 1687-1695 (1998).
107. Bosque, F., Saravia, N. G., Valderrama, L. & Milan, G. Distinct innate and acquired immune responses to Leishmania in putative susceptible and resistant human populations endemically exposed to L. (Viannia) panamensis infection. Scand. J. Immunol. 51, 533-541 (2000).
108. Kemp, K. et al. Leishmania-specific T cells expressing interferon-γ (IFN-γ) and IL-10 upon activation are expanded in individuals cured of visceral leishmaniasis. Clin. Exp. Immunol. 116, 500-504 (1999).
109. + immunoregulatory T lymphocytes control Leishmania major persistence and the development of concomitant immunity. Nature (in the press).
110. Uzonna, J. E., Wei, G., Yurkowski, D. & Bretscher, P. Immune elimination of Leishmania major in mice: implications for immune memory, vaccination and reactivation disease. J. Immunol. 167, 6967-6974 (2001). The first indication that sterile cure results in the loss of immunity to re-infection.
111. Modabber, F. Experiences with vaccines against cutaneous leishmaniasis: of men and mice. Parasitology 98, S49-S60 (1989).
112. Sharifi, I. et al. Randomised vaccine trial of single dose of killed Leashmania major plus BCG against anthroponotic cutaneous leishmaniasis in Bam, Iran. Lancet 351, 1540-1543 (1998).
113. Momeni, A. Z. et al. A randomised, double-blind, controlled trial of a killed L. major vaccine plus BCG against zoonotic cutaneous leishmaniasis in Iran. Vaccine 17, 466-472 (1999).
114. Gurunathan, S., Prussin, C., Sacks, D. L. & Seder, R. A. Vaccine requirements for sustained cellular immunity to an intracellular parasitic infection. Nature Med. 4, 1409-1415 (1998). A demonstration that long-lasting vaccine-induced protection requires persistent antigen and IL-12.
115. Mendez, S. et al. The potency and durability of DNA- and protein-based vaccines against Leishmania major evaluated using low-dose, intradermal challenge. J. Immunol. 166, 5122-5128 (2001).
116. Seder, R. A. & Hill, A. V. Vaccines against intracellular Infections requiring cellular immunity. Nature 406, 793-798 (2000).
117. Gillespie, R. D., Mbow, M. L. & Titus, R. G. The immunomodulatory factors of bloodfeeding arthropod Saliva. Parasite Immunol. 22, 319-331 (2000).
118. Belkaid, Y. et al. Development of a natural model of cutaneous leishmaniasis: powerful effects of vector saliva and saliva preexposure on the long-term outcome of Leishmania major infection in the mouse ear dermis. J. Exp. Med. 188, 1941-1953 (1998).
119. Kamhawi, S., Belkaid, Y., Modi, G., Rowton, E. & Sacks, D. Protection against cutaneous leishmaniasis resulting from bites of uninfected sand files. Science 290, 1351-1354 (2000). A demonstration that the immune response to sandfly saliva can potentiate the host response to L. major infection transmitted by sandfly bite.
120. Valenzuela, J. G. et al. Toward a defined anti-Leishmania vaccine targeting vector antigens: characterization of a protective salivary protein. J. Exp. Med. 194, 331-342 (2001).
121. Morris, R. V., Shoemaker, C. B., David, J. R., Lanzaro, G. C. & Titus, R. G. Sandfly maxadilan exacerbates infection with Leishmania major and vaccinating against it protects against L. major infection. J. Immunol. 167, 5226-5230 (2001).
122. Sacks, D. L., Hieny, S. & Sher, A. Identification of cell-surface carbohydrate and antigenic changes between noninfective and infective developmental stages of Leishmania major promastigotes. J. Immunol. 135, 564-569 (1985).
123. Kellina, O. I. Differences in the sensitivity of inbred mice of different lines to Leishmania tropica major. Med. Parazitol. (Mosk.) 42, 279-285 (1973).
124. Nasseri, M. & Modabber, F. Z. Generalized infection and lack of delayed hypersensitivity in BALB/c mice infected with Leishmania tropica major. Infect. Immun. 26, 611-614 (1979).
125. Howard, J. G., Hale, C. & Liew, F. Y. Immunological regulation of experimental cutaneous leishmaniasis. III. Nature and significance of specific suppression of cell-mediated immunity in mice highly susceptible to Leishmania tropica. J. Exp. Med. 152, 594-607 (1980).
126. Mosmann, T. R., Cherwinski, H., Bond, M. W., Giedlin, M. A. & Coffman, R. L. Two types of murine helper T-cell clones. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 136, 2348-2357 (1986).
127. Scott, P., Natovitz, P., Coffman, R. L., Pearce, E. & Sher, A. Immunoregulation of cutaneous leishmaniasis. T-cell lines that transfer protective immunity or exacerbation belong to different T-helper subsets and respond to distinct parasite antigens. J. Exp. Med. 188, 1675-1684 (1988).
128. Heinzel, F. P., Sadick, M. D., Holaday, B. J., Coffman, R. L. & Locksley, R. M. Reciprocal expression of interferon-γ or interleukin-4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T-cell subsets. J. Exp. Med. 169, 59-72 (1989).
129. Mock, B., Blackwell, J., Hilgers, J., Potter, M. & Nacy, C. Genetic control of Leishmania major infection in congenic, recombinant inbred and F2 populations of mice. Eur. J. Immunogenet. 20, 335-348 (1993).
130. Yang, D. M. et al. Oral Salmonella typhimurium (AroA-) vaccine expressing a major leishmanial surface protein (gp63) preferentially induces T helper 1 cells and protective immunity against leishmaniasis. J. Immunol. 145, 2281-2285 (1990).
131. Connell, N. D., Medina-Acosta, E., McMaster, W. R., Bloom, B. R. & Russell, D. G. Effective immunization against cutaneous leishmaniasis with recombinant bacille Calmette-Guerin expressing the Leishmania surface proteinase gp63. Proc. Natl Acad. Sci. USA 90, 11473-11477 (1993).
132. Spitzer, N., Jardim, A., Lippert, D. & Olafson, R. W. Long-term protection of mice against Leishmania major with a synthetic peptide vaccine. Vaccine 17, 1298-1300 (1999).
133. Xu, D. & Liew, F. Y. Protection against leishmaniasis by injection of DNA encoding a major surface glycoprotein, gp63, of L. major. Immunology 84, 173-176 (1995).
134. H1 type of immune response. Infect. Immun. 63, 4261-4267 (1995).
135. H2 response are required for generation of immunity to leishmaniasis. J. Immunol. 160, 3949-3957 (1998).
136. Mougneau, E. et al. Expression cloning of a protective Leishmania antigen. Science 268, 563-566 (1995).
137. Webb, J. R. et al. Human and murine immune responses to a novel Leishmania major recombinant protein encoded by members of a multicopy gene family. Infect. Immun. 66, 3279-3289 (1998).
138. Campos-Neto, A. et al. Vaccination with plasmid DNA encoding TSA/LmSTI1 leishmanial fusion proteins confers protection against Leishmania major infection in susceptible BALB/c mice. Infect. Immun. 70, 2828-2836 (2002).
139. Rafati, S., Salmanian, A. H., Taheri, T., Vafa, M. & Fasel, N. A protective cocktail vaccine against murine cutaneous leishmaniasis with DNA encoding cysteine proteinases of Leishmania major. Vaccine 19, 3369-3375 (2001).
140. Solioz, N. et al. The protective capacities of histone H1 against experimental murine cutaneous leishmaniasis. Vaccine 18, 850-859 (1999).