Protection of athymic (Nu/Nu) BALB/c mice against Plasmodium berghei by splenocytes from normal (Nu/ +) BALB/c mice

Ferraroni, José J.; Douglass, Thomas G.; Speer, Clarence A.

doi:10.1590/S0036-46651985000600003

Abstracts

Athymic BALB/c (Nu/Nu) mice died at 7-13 days after inoculation (DAI) of Plasmodium berghei NK65, whereas their heterozygous (Nu/+) littermates died at 7-8 DAI. Nude (Nu/Nu) mice, reconstituted with 2 x 10(7) splenocytes from uninfected heterozygous (Nu/+) littermates at 20 days before parasite inoculation (DBI), died about 2 days earlier than control nude mice; nude mice reconstituted at 10 or 2 DBI lived 2 to 4 days longer than control nudes; and nude mice reconstituted 2 DAI lived even longer and some survived. These findings indicate that P. berghei NK65 induces at least two T-cell dependent immune phenomena, one suppressive and the other stimulatory. Reconstitution of nude mice with T-cells from BALB/c (Nu/+) mice appeared to reduce or bypass suppressive T-cell activities which allowed the formation of a protective immune response by some of the nude mice.

Camundongos atímicos BALB/c (Nu/Nu) sucumbem entre 7-13 dias após a inoculação (DAI) da cepa NK65 de Plasmodium berghei. Todavia, seus singenêicos heterozigotos (Nu/+) morrem em 7-8 DAI. Camundongos nude (Nu/Nu) reconstituídos com 2xl0(7) esplenócitos de camundongos heterozigotos singenêicos normais não infectados (Nu/+) 20 dias antes da inoculação a (DBI) do parasita, sucumbem 2 dias antes que os animais controles. Camundongos nude reconstituídos 10 ou 2 DBI, vivem 2-4 dias a mais que os animais controles e alguns deles sobrevivem. Esses achados indicam que a cepa NK65 de P. berghei induz, no mínimo, dois imunofenômenos dependentes de linfócitos T; um supressivo e outro estimulatório. A reconstituição de camundongos nude com células T de camundongos BALB/c (Nu/+) parece reduzir ou "By-pass" a atividade supressora das células T, o qual leva à formação de uma resposta imune protetora por alguns dos camundongos nude.

ORIGINAL ARTICLES

Protection of athymic (Nu/Nu) BALB/c mice against Plasmodium berghei by splenocytes from normal (Nu/ +) BALB/c mice (^{^*} (* ) This study is based on a dissertation submitted by J. J. Perraroni to the Graduate School of the University of Montana in partial fulfillment to the requirements for the Doctor of Philosophy degree )

Proteção de camundongos atímicos BALB/c (Nu/Nu) contra Plasmodium berghei por esplenócitos oriundos de camundongos normais BALB/c (Nu/+)

José J. Ferraroni^{I, II}; Thomas G. Douglass^II; Clarence A. Speer^III

^IUniversidade do Amazonas/CNPq, Campus Universitário, Departamento de Patologia ICB 69.000, Manaus, Amazonas, Brasil

^IIDepartment of Microbiology, University of Montana, Missoula, Montana, 59812 USA

SUMMARY

Athymic BALB/c (Nu/Nu) mice died at 7-13 days after inoculation (DAI) of Plasmodium berghei NK65, whereas their heterozygous (Nu/+) littermates died at 7-8 DAI. Nude (Nu/Nu) mice, reconstituted with 2 x 10⁷ splenocytes from uninfected heterozygous (Nu/+) littermates at 20 days before parasite inoculation (DBI), died about 2 days earlier than control nude mice; nude mice reconstituted at 10 or 2 DBI lived 2 to 4 days longer than control nudes; and nude mice reconstituted 2 DAI lived even longer and some survived. These findings indicate that P. berghei NK65 induces at least two T-cell dependent immune phenomena, one suppressive and the other stimulatory. Reconstitution of nude mice with T-cells from BALB/c (Nu/+) mice appeared to reduce or bypass suppressive T-cell activities which allowed the formation of a protective immune response by some of the nude mice.

RESUMO

Camundongos atímicos BALB/c (Nu/Nu) sucumbem entre 7-13 dias após a inoculação (DAI) da cepa NK65 de Plasmodium berghei. Todavia, seus singenêicos heterozigotos (Nu/+) morrem em 7-8 DAI. Camundongos nude (Nu/Nu) reconstituídos com 2xl0⁷ esplenócitos de camundongos heterozigotos singenêicos normais não infectados (Nu/+) 20 dias antes da inoculação a (DBI) do parasita, sucumbem 2 dias antes que os animais controles. Camundongos nude reconstituídos 10 ou 2 DBI, vivem 2-4 dias a mais que os animais controles e alguns deles sobrevivem. Esses achados indicam que a cepa NK65 de P. berghei induz, no mínimo, dois imunofenômenos dependentes de linfócitos T; um supressivo e outro estimulatório. A reconstituição de camundongos nude com células T de camundongos BALB/c (Nu/+) parece reduzir ou "By-pass" a atividade supressora das células T, o qual leva à formação de uma resposta imune protetora por alguns dos camundongos nude.

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1. BAZAR-MALIK, G. Increased resistance to malaria after Mycobacterium tuberculosis infection. Indian J. Med. Res. 61: 1014-1024, 1973.
2. BERGHE, V. D. 4th International Cong. Malaria and Tropical Medicine (1948). In R. Killick-Kendrick and W. Peters (eds). Rodent Malaria. London, Academic Press, 1978.
3. BROWN, I. N. Immunological aspects of malaria infection. Advan. Immunol. 11: 267-349, 1970.
4. CAULEY, L. K. & MURPHY, J. W. Response of congenitally athymic (nude) and phenotypically normal mice to Cryptococcus neoformans infection. Infect. Immun. 23: 644-651, 1979.
5. CHEERS, C. & WALLER, R. Activated macrophages in congenitally athymic "nude" mice and in lenthally irradiated mice. J. Immunol. 115: 844-847, 1975.
6. CLARK, I. A.; ALLISON, A. C. & COX, P. E. G. Protection of mice against Babesia and Plasmodium with BCG. Nature (London) 259: 309-311, 1976.
7. CLARK, I. A.; COX, P. E. G. & ALLISON, A. C. Protection of mice against Babesia spp and Plasmodium spp with killed Corynebacterium parvum. Parasitology 74: 9-18, 1977.
8. ELING, W. Fading of malaria immunity in mice. Z. tropenmed. Parasitol. 29: 77-84, 1978.
9. EMMERLING, P.; FINGER, H. & BOCKEMUHL, J. Listeria monocytogenes infection in nude mice. Infect. Immun. 12: 437-439, 1975.
10. FAUVE, R. M. & HEVIN, B. Resistance paradoxale des sours thymoprives a l'infection pas Listeria monocytogenes et Salmonella typhimurium et action immunostimulante d'un bacterien phospholipidique (EBP). C. R. Acad. Sci. 279: 1603-1605, 1974.
11. FERRARONI, J. J. & SPEER, C. A. Fansidar prophylaxis, therapy and immune responses in rodent malaria (Plasmodium berghei). J. Parasitol. 68: 609-615, 1981.
12. FERRARONI, J. J. & SPEER, C. A. Adotive transfer of resistance to Plasmodium berghei with spleen cells and serum from Fansidar-cured mice. Infect. Immun. 36: 1109-1114, 1981.
13. GREENBERG, J. & KENDRICK, L. P. Some characteristics of Plasmodium berghei passed within inbred strains of mice. J. Parasitol. 43: 420-427, 1967.
14. HAAIJMAN, J. J.; TEUNISSEN, J. S.; OUDENAREN, A. V.; MINK, J. G. & BENNER, R. Kinetics of recovery of serum Ig levels and of cytoplasmic Ig positive cells in various, lymphoid organs of nude mice after thymus transplantation. Immunology 41: 279-287, 1980.
15. JAHIEL, R. I.; VILCEK, J.; NUSSENZWEIG, R. S, & VANDERBERG, J. Interferon inducers protect mice against Plasmodium berghei malaria. Science 161: 802-804, 1968.
16. JAHIEL, R. I.; NUSSENZWEIG, R. S. ; VILCET, J. & VANDERBERG, J. Protective effect of interferon inducers of Plasmodium berghei malaria. Am. J. Trop. Med. Hyg. 18: 823-835, 1969.
17. JAHIEL, R. I.; NUSSENZWEIG, R. S.; VILCET, J. & VANDERBERG, J. Anti-malarial effect of interferon inducers at different stages of development of Plasmodium berghei in the mouse. Nature (London) 220: 710-711, 1968.
18. KILLICK-KENDRICK, R. Parasitic Protozoa of the blood of rodents: A revision of Plasmodium berghei Parasitology 66: 225-237, 1974.
19. LAIR, S. V. & LOZZIO, B. B. Thymocyte reconstitution of athymic and athymic-asplenic mice: Graft rejection and antibody synthesis. Exp. Cell Biol. 48: 439-444, 1980.
20. METCALF, E. ; SCHEATER, A. F. & KLINMAN, N. R. Murine models of tolerance induction in developing and mature B cells. Immunol. Rev. 43: 143-183, 1979.
21. MONGENSEN, S. C. & ANDERSEN, H. K. Role of activated macrophages in resistance of congenitally athymic nude mice to hepatitis induced by herpes simplex virus type 2. Infect. Immun. 19: 792-798, 1978.
22. MURPHY, J. R. Host defenses in murine malaria: Nonspecific resistance of Plasmodium berghei genera- ted in response to Mycobacterium bovis infection or Corynebacterium parvum stimulation. Infect. Immun. 33: 199-211, 1981.
23. NICKOL, A. D. & BON VENTRE, P. F. Anomalous high native resistance of athymic mice to bacterial pathogens. Infect. Immun. 18: 636-645, 1977.
24. NUSSENZWEIG, R. S. Increased nonspecific resistance to malaria produced by administration of kililed Corynebacterium parvum. Exp. Parasitol. 21: 224-231, 1967.
25. NUSSENZWEIG, R. S.; VANDERBERG, J. & MOST, H. Protective immunity produced by the injection of X-irradiated sporozoites of Plasmodium berghei IV. Dose response, especific and humoral immunity. Milit. Med. 134: 1176-1182, 1969.
26. PRAKASHI, S. Studies on Plasmodium berghei Vincke and Lips, 1948. XXVII. Duration of patent primary parasitemia necessary for the development of measurable acquired immunity, if any, in the albino mice. Indian J. Malariol. 14: 165-170, 1960.
27. REID, V. E. & FRIEDKIN, M. Plasmodium berghei: Folic acid levels in mouse erythrocytes. Exp. Parasitol. 33: 424-428, 1973.
23. ROGER, T. J.; BALISH, E. & MANNING, D. D. The role of cell mediated immunity in resistance to experimental candidiasis. J. Reticuloendothel. Soc. 20: 291-298, 1976.
29. SCHRADER, J. W. The role of T cells in IgG production: Thymus-dependent antigens induce B cell memory in the absence of T cells. J. Immunol. 114: 1665-1669, 1975.
30. SHULTZ, W. W.; HUANG, K. Y. & GORDON, F. B. Role of interferon in experimental mouse malaria. Nature (London) 220: 709-710, 1968.
31. SMRKOVSKI, L. L. & STRICKLAND, G. T. Rodent malaria: BCG-induced protection and immunosuppression. J. Immunol. 121: 1257-1261, 1978.
32. SOUZA, M. de & PRITCHARD, H. The cellular basis of immunological recovery in nude mice after thymus grafting. Immunology 26: 769-776, 1974.
33. TANABE, K.; WAKI, S.; TAKADA, S. & SUZUKI, M. Plasmodium berghei: Suppressed response of anti-body-forming cells in the infected mice. Exp. Pararasitol. 43: 143-152, 1977.
34. TAVERNE, J.; DOCKRELL, H. M. & PLAYFAIR, J. H. Endotoxin-induced serum factor kills malarial parasites in vitro. Infect. Immun. 33: 83-89, 1981.
35. TOBIE, J. E.; WOLF, S. M. & JEFFERY, G. M. Immune response of man to inoculation with Plasmodium cynomolgi and challenge with Plasmodium vivax. Lancet 2: 300-303, 1966.
36. TUBES, H. Endotoxin in human and murine malaria. Trans. Roy. Soc. Trop. Med. Hyg. 74: 121-123, 1980.
37. WAKI, S. Protective immunity of Plasmodium berghei in mice induced by repeated infection and chemotherapy. Japan. J. Parasitol. 6: 441-446, 1976.
38. WAKI, S. & SUZUKI, M. A study of malaria immunobiology using nude mice. In Proceedings of the 2nd International Workshop on nude mice. University Tokyo Press, p. 37. Stuttgart, Gustav Fisher Verlag, 1977.
39. WAKI, S. & SUZUKI, M. T-independent antibody production in nude mice immunized with a rodent malaria parasite (Plasmodium berghei). In N. D. Reed (ed.). Proceedings of the 3rd Internation Workshop on nude mice. New York, Gustav Fisher, 1981.
40. WARD, J. M.; COLLINS, M. J. & PARKER, J. C. Natural occurring hepatitis virus infection in the nude mouse. Lab. Anim. Sci. 27: 372-376, 1977.
41. WEINTRAUBE, M. Interferon in malaria. Ann. Int. Med. 37: 1045, 1970.

(*

) This study is based on a dissertation submitted by J. J. Perraroni to the Graduate School of the University of Montana in partial fulfillment to the requirements for the Doctor of Philosophy degree

Publication Dates

Publication in this collection
25 Oct 2012
Date of issue
Dec 1985

History

Received
16 Nov 1983

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. BAZAR-MALIK, G. Increased resistance to malaria after Mycobacterium tuberculosis infection. Indian J. Med. Res. 61: 1014-1024, 1973.

[2] 2. BERGHE, V. D. 4th International Cong. Malaria and Tropical Medicine (1948). In R. Killick-Kendrick and W. Peters (eds). Rodent Malaria. London, Academic Press, 1978.

[3] 3. BROWN, I. N. Immunological aspects of malaria infection. Advan. Immunol. 11: 267-349, 1970.

[4] 4. CAULEY, L. K. & MURPHY, J. W. Response of congenitally athymic (nude) and phenotypically normal mice to Cryptococcus neoformans infection. Infect. Immun. 23: 644-651, 1979.

[5] 5. CHEERS, C. & WALLER, R. Activated macrophages in congenitally athymic "nude" mice and in lenthally irradiated mice. J. Immunol. 115: 844-847, 1975.

[6] 6. CLARK, I. A.; ALLISON, A. C. & COX, P. E. G. Protection of mice against Babesia and Plasmodium with BCG. Nature (London) 259: 309-311, 1976.

[7] 7. CLARK, I. A.; COX, P. E. G. & ALLISON, A. C. Protection of mice against Babesia spp and Plasmodium spp with killed Corynebacterium parvum. Parasitology 74: 9-18, 1977.

[8] 8. ELING, W. Fading of malaria immunity in mice. Z. tropenmed. Parasitol. 29: 77-84, 1978.

[9] 9. EMMERLING, P.; FINGER, H. & BOCKEMUHL, J. Listeria monocytogenes infection in nude mice. Infect. Immun. 12: 437-439, 1975.

[10] 10. FAUVE, R. M. & HEVIN, B. Resistance paradoxale des sours thymoprives a l'infection pas Listeria monocytogenes et Salmonella typhimurium et action immunostimulante d'un bacterien phospholipidique (EBP). C. R. Acad. Sci. 279: 1603-1605, 1974.

[11] 11. FERRARONI, J. J. & SPEER, C. A. Fansidar prophylaxis, therapy and immune responses in rodent malaria (Plasmodium berghei). J. Parasitol. 68: 609-615, 1981.

[12] 12. FERRARONI, J. J. & SPEER, C. A. Adotive transfer of resistance to Plasmodium berghei with spleen cells and serum from Fansidar-cured mice. Infect. Immun. 36: 1109-1114, 1981.

[13] 13. GREENBERG, J. & KENDRICK, L. P. Some characteristics of Plasmodium berghei passed within inbred strains of mice. J. Parasitol. 43: 420-427, 1967.

[14] 14. HAAIJMAN, J. J.; TEUNISSEN, J. S.; OUDENAREN, A. V.; MINK, J. G. & BENNER, R. Kinetics of recovery of serum Ig levels and of cytoplasmic Ig positive cells in various, lymphoid organs of nude mice after thymus transplantation. Immunology 41: 279-287, 1980.

[15] 15. JAHIEL, R. I.; VILCEK, J.; NUSSENZWEIG, R. S, & VANDERBERG, J. Interferon inducers protect mice against Plasmodium berghei malaria. Science 161: 802-804, 1968.

[16] 16. JAHIEL, R. I.; NUSSENZWEIG, R. S. ; VILCET, J. & VANDERBERG, J. Protective effect of interferon inducers of Plasmodium berghei malaria. Am. J. Trop. Med. Hyg. 18: 823-835, 1969.

[17] 17. JAHIEL, R. I.; NUSSENZWEIG, R. S.; VILCET, J. & VANDERBERG, J. Anti-malarial effect of interferon inducers at different stages of development of Plasmodium berghei in the mouse. Nature (London) 220: 710-711, 1968.

[18] 18. KILLICK-KENDRICK, R. Parasitic Protozoa of the blood of rodents: A revision of Plasmodium berghei Parasitology 66: 225-237, 1974.

[19] 19. LAIR, S. V. & LOZZIO, B. B. Thymocyte reconstitution of athymic and athymic-asplenic mice: Graft rejection and antibody synthesis. Exp. Cell Biol. 48: 439-444, 1980.

[20] 20. METCALF, E. ; SCHEATER, A. F. & KLINMAN, N. R. Murine models of tolerance induction in developing and mature B cells. Immunol. Rev. 43: 143-183, 1979.

[21] 21. MONGENSEN, S. C. & ANDERSEN, H. K. Role of activated macrophages in resistance of congenitally athymic nude mice to hepatitis induced by herpes simplex virus type 2. Infect. Immun. 19: 792-798, 1978.

[22] 22. MURPHY, J. R. Host defenses in murine malaria: Nonspecific resistance of Plasmodium berghei genera- ted in response to Mycobacterium bovis infection or Corynebacterium parvum stimulation. Infect. Immun. 33: 199-211, 1981.

[23] 23. NICKOL, A. D. & BON VENTRE, P. F. Anomalous high native resistance of athymic mice to bacterial pathogens. Infect. Immun. 18: 636-645, 1977.

[24] 24. NUSSENZWEIG, R. S. Increased nonspecific resistance to malaria produced by administration of kililed Corynebacterium parvum. Exp. Parasitol. 21: 224-231, 1967.

[25] 25. NUSSENZWEIG, R. S.; VANDERBERG, J. & MOST, H. Protective immunity produced by the injection of X-irradiated sporozoites of Plasmodium berghei IV. Dose response, especific and humoral immunity. Milit. Med. 134: 1176-1182, 1969.

[26] 26. PRAKASHI, S. Studies on Plasmodium berghei Vincke and Lips, 1948. XXVII. Duration of patent primary parasitemia necessary for the development of measurable acquired immunity, if any, in the albino mice. Indian J. Malariol. 14: 165-170, 1960.

[27] 27. REID, V. E. & FRIEDKIN, M. Plasmodium berghei: Folic acid levels in mouse erythrocytes. Exp. Parasitol. 33: 424-428, 1973.

[28] 23. ROGER, T. J.; BALISH, E. & MANNING, D. D. The role of cell mediated immunity in resistance to experimental candidiasis. J. Reticuloendothel. Soc. 20: 291-298, 1976.

[29] 29. SCHRADER, J. W. The role of T cells in IgG production: Thymus-dependent antigens induce B cell memory in the absence of T cells. J. Immunol. 114: 1665-1669, 1975.

[30] 30. SHULTZ, W. W.; HUANG, K. Y. & GORDON, F. B. Role of interferon in experimental mouse malaria. Nature (London) 220: 709-710, 1968.

[31] 31. SMRKOVSKI, L. L. & STRICKLAND, G. T. Rodent malaria: BCG-induced protection and immunosuppression. J. Immunol. 121: 1257-1261, 1978.

[32] 32. SOUZA, M. de & PRITCHARD, H. The cellular basis of immunological recovery in nude mice after thymus grafting. Immunology 26: 769-776, 1974.

[33] 33. TANABE, K.; WAKI, S.; TAKADA, S. & SUZUKI, M. Plasmodium berghei: Suppressed response of anti-body-forming cells in the infected mice. Exp. Pararasitol. 43: 143-152, 1977.

[34] 34. TAVERNE, J.; DOCKRELL, H. M. & PLAYFAIR, J. H. Endotoxin-induced serum factor kills malarial parasites in vitro. Infect. Immun. 33: 83-89, 1981.

[35] 35. TOBIE, J. E.; WOLF, S. M. & JEFFERY, G. M. Immune response of man to inoculation with Plasmodium cynomolgi and challenge with Plasmodium vivax. Lancet 2: 300-303, 1966.

[36] 36. TUBES, H. Endotoxin in human and murine malaria. Trans. Roy. Soc. Trop. Med. Hyg. 74: 121-123, 1980.

[37] 37. WAKI, S. Protective immunity of Plasmodium berghei in mice induced by repeated infection and chemotherapy. Japan. J. Parasitol. 6: 441-446, 1976.

[38] 38. WAKI, S. & SUZUKI, M. A study of malaria immunobiology using nude mice. In Proceedings of the 2nd International Workshop on nude mice. University Tokyo Press, p. 37. Stuttgart, Gustav Fisher Verlag, 1977.

[39] 39. WAKI, S. & SUZUKI, M. T-independent antibody production in nude mice immunized with a rodent malaria parasite (Plasmodium berghei). In N. D. Reed (ed.). Proceedings of the 3rd Internation Workshop on nude mice. New York, Gustav Fisher, 1981.

[40] 40. WARD, J. M.; COLLINS, M. J. & PARKER, J. C. Natural occurring hepatitis virus infection in the nude mouse. Lab. Anim. Sci. 27: 372-376, 1977.

[41] 41. WEINTRAUBE, M. Interferon in malaria. Ann. Int. Med. 37: 1045, 1970.

Brasil

Brasil

Protection of athymic (Nu/Nu) BALB/c mice against Plasmodium berghei by splenocytes from normal (Nu/ +) BALB/c mice

Proteção de camundongos atímicos BALB/c (Nu/Nu) contra Plasmodium berghei por esplenócitos oriundos de camundongos normais BALB/c (Nu/+)

Abstracts

Publication Dates

History