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. 1996 Aug;64(8):2962–2967. doi: 10.1128/iai.64.8.2962-2967.1996

Th1-like antifilarial immune responses predominate in antigen-negative persons.

K A Dimock 1, M L Eberhard 1, P J Lammie 1
PMCID: PMC174175  PMID: 8757821

Abstract

To characterize immune responses associated with the putatively immune state in bancroftian filariasis (that is, both microfilaria and antigen free), humoral and cellular responses were compared among antigen- and microfilaria-negative, antigen-positive and microfilaria-negative, and microfilaria-positive individuals. Antifilarial isotype levels were measured by enzyme-linked immunosorbent assay. Peripheral blood mononuclear cell responses were measured by proliferation, by bioassay for interleukin-2 (IL-2) and IL-10, and by reverse transcription-PCR for IL-4, IL-5, and gamma interferon. The absence of circulating filarial antigen was associated with Th1-like responses, including significantly higher proliferative (P < 0.001) and IL-2 (P = 0.008) responses and a higher prevalence of gamma interferon (0.02 < P < 0.1) responses. Significantly elevated antifilarial immunoglobulin G4 (IgG4) levels (P = 0.0035) were associated with antigenemia, whereas microfilaremia was associated with significantly decreased antifilarial IgG2 levels (P = 0.0014). IL-4 mRNA levels were not significantly different among the three groups; however, there was a subpopulation of microfilaremic individuals who did not make detectable levels of IL-4 mRNA and who produced low antifilarial IgG4 levels compared with those of individuals who had detectable levels of IL-4 mRNA. IL-5 mRNA levels also were not significantly different among groups; however, more microfilaremic individuals produced IL-5 mRNA in response to adult filarial antigens, and total parasite-specific IL-4 and IL-5 mRNA levels were significantly correlated (P = 0.05). Although longitudinal data are not currently available, the elevated Th1-like responses in antigen- and microfilaria-negative individuals are consistent with the hypothesis that these responses contribute to protection in putatively immune individuals.

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Selected References

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  1. Addiss D. G., Dimock K. A., Eberhard M. L., Lammie P. J. Clinical, parasitologic, and immunologic observations of patients with hydrocele and elephantiasis in an area with endemic lymphatic filariasis. J Infect Dis. 1995 Mar;171(3):755–758. doi: 10.1093/infdis/171.3.755. [DOI] [PubMed] [Google Scholar]
  2. Assenmacher M., Schmitz J., Radbruch A. Flow cytometric determination of cytokines in activated murine T helper lymphocytes: expression of interleukin-10 in interferon-gamma and in interleukin-4-expressing cells. Eur J Immunol. 1994 May;24(5):1097–1101. doi: 10.1002/eji.1830240513. [DOI] [PubMed] [Google Scholar]
  3. Bailey J. W., Hightower A. W., Eberhard M. L., Lammie P. J. Acquisition and expression of humoral reactivity to antigens of infective stages of filarial larvae. Parasite Immunol. 1995 Dec;17(12):617–623. doi: 10.1111/j.1365-3024.1995.tb01007.x. [DOI] [PubMed] [Google Scholar]
  4. Chanteau S., Moulia-Pelat J. P., Glaziou P., Nguyen N. L., Luquiaud P., Plichart C., Martin P. M., Cartel J. L. Og4C3 circulating antigen: a marker of infection and adult worm burden in Wuchereria bancrofti filariasis. J Infect Dis. 1994 Jul;170(1):247–250. doi: 10.1093/infdis/170.1.247. [DOI] [PubMed] [Google Scholar]
  5. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  6. Day K. P., Gregory W. F., Maizels R. M. Age-specific acquisition of immunity to infective larvae in a bancroftian filariasis endemic area of Papua New Guinea. Parasite Immunol. 1991 May;13(3):277–290. doi: 10.1111/j.1365-3024.1991.tb00282.x. [DOI] [PubMed] [Google Scholar]
  7. Day K. P. The endemic normal in lymphatic filariasis: A static concept. Parasitol Today. 1991 Dec;7(12):341–343. doi: 10.1016/0169-4758(91)90215-a. [DOI] [PubMed] [Google Scholar]
  8. Denham D. A., McGreevy P. B., Suswillo R. R., Rogers R. The resistance to re-infection of cats repeatedly inoculated with infective larvae of Brugia pahangi. Parasitology. 1983 Feb;86(Pt 1):11–18. doi: 10.1017/s0031182000057127. [DOI] [PubMed] [Google Scholar]
  9. Dimock K. A., Addiss D. G., Eberhard M. L., Lammie P. J. Differential proliferative and interleukin-10 responses to fractionated filarial antigens: preferential recognition by patients with chronic lymphatic dysfunction. J Infect Dis. 1994 Aug;170(2):403–412. doi: 10.1093/infdis/170.2.403. [DOI] [PubMed] [Google Scholar]
  10. Elson L. H., Calvopiña M., Paredes W., Araujo E., Bradley J. E., Guderian R. H., Nutman T. B. Immunity to onchocerciasis: putative immune persons produce a Th1-like response to Onchocerca volvulus. J Infect Dis. 1995 Mar;171(3):652–658. doi: 10.1093/infdis/171.3.652. [DOI] [PubMed] [Google Scholar]
  11. Farrar M. A., Schreiber R. D. The molecular cell biology of interferon-gamma and its receptor. Annu Rev Immunol. 1993;11:571–611. doi: 10.1146/annurev.iy.11.040193.003035. [DOI] [PubMed] [Google Scholar]
  12. Finkelman F. D., Pearce E. J., Urban J. F., Jr, Sher A. Regulation and biological function of helminth-induced cytokine responses. Immunol Today. 1991 Mar;12(3):A62–A66. doi: 10.1016/S0167-5699(05)80018-0. [DOI] [PubMed] [Google Scholar]
  13. Freedman D. O., Nutman T. B., Ottesen E. A. Protective immunity in bancroftian filariasis. Selective recognition of a 43-kD larval stage antigen by infection-free individuals in an endemic area. J Clin Invest. 1989 Jan;83(1):14–22. doi: 10.1172/JCI113850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Grenfell B. T., Michael E., Denham D. A. A model for the dynamics of human lymphatic filariasis. Parasitol Today. 1991 Nov;7(11):318–323. doi: 10.1016/0169-4758(91)90270-x. [DOI] [PubMed] [Google Scholar]
  15. Grenfell B. T., Michael E. Infection and disease in lymphatic filariasis: an epidemiological approach. Parasitology. 1992;104 (Suppl):S81–S90. doi: 10.1017/s0031182000075260. [DOI] [PubMed] [Google Scholar]
  16. Hitch W. L., Hightower A. W., Eberhard M. L., Lammie P. J. Analysis of isotype-specific antifilarial antibody levels in a Haitian pediatric population. Am J Trop Med Hyg. 1991 Feb;44(2):161–167. doi: 10.4269/ajtmh.1991.44.161. [DOI] [PubMed] [Google Scholar]
  17. Hussain R., Grögl M., Ottesen E. A. IgG antibody subclasses in human filariasis. Differential subclass recognition of parasite antigens correlates with different clinical manifestations of infection. J Immunol. 1987 Oct 15;139(8):2794–2798. [PubMed] [Google Scholar]
  18. Kelso A., Groves P., Troutt A. B., Francis K. Evidence for the stochastic acquisition of cytokine profile by CD4+ T cells activated in a T helper type 2-like response in vivo. Eur J Immunol. 1995 May;25(5):1168–1175. doi: 10.1002/eji.1830250506. [DOI] [PubMed] [Google Scholar]
  19. Kelso A. Th1 and Th2 subsets: paradigms lost? Immunol Today. 1995 Aug;16(8):374–379. doi: 10.1016/0167-5699(95)80004-2. [DOI] [PubMed] [Google Scholar]
  20. King C. L., Mahanty S., Kumaraswami V., Abrams J. S., Regunathan J., Jayaraman K., Ottesen E. A., Nutman T. B. Cytokine control of parasite-specific anergy in human lymphatic filariasis. Preferential induction of a regulatory T helper type 2 lymphocyte subset. J Clin Invest. 1993 Oct;92(4):1667–1673. doi: 10.1172/JCI116752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. King C. L., Nutman T. B. Regulation of the immune response in lymphatic filariasis and onchocerciasis. Immunol Today. 1991 Mar;12(3):A54–A58. doi: 10.1016/S0167-5699(05)80016-7. [DOI] [PubMed] [Google Scholar]
  22. Lammie P. J., Hightower A. W., Eberhard M. L. Age-specific prevalence of antigenemia in a Wuchereria bancrofti-exposed population. Am J Trop Med Hyg. 1994 Sep;51(3):348–355. doi: 10.4269/ajtmh.1994.51.348. [DOI] [PubMed] [Google Scholar]
  23. Lammie P. J., Katz S. P. Immunoregulation in experimental filariasis. II. Responses to parasite and nonparasite antigens in jirds with Brugia pahangi. J Immunol. 1983 Mar;130(3):1386–1389. [PubMed] [Google Scholar]
  24. Mahanty S., Abrams J. S., King C. L., Limaye A. P., Nutman T. B. Parallel regulation of IL-4 and IL-5 in human helminth infections. J Immunol. 1992 Jun 1;148(11):3567–3571. [PubMed] [Google Scholar]
  25. Maizels R. M., Lawrence R. A. Immunological tolerance: The key feature in human filariasis? Parasitol Today. 1991 Oct;7(10):271–276. doi: 10.1016/0169-4758(91)90093-4. [DOI] [PubMed] [Google Scholar]
  26. Maizels R. M., Sartono E., Kurniawan A., Partono F., Selkirk M. E., Yazdanbakhsh M. T-cell activation and the balance of antibody isotypes in human lymphatic filariasis. Parasitol Today. 1995 Feb;11(2):50–56. doi: 10.1016/0169-4758(95)80116-2. [DOI] [PubMed] [Google Scholar]
  27. Marley S. E., Lammie P. J., Eberhard M. L., Hightower A. W. Reduced antifilarial IgG4 responsiveness in a subpopulation of microfilaremic persons. J Infect Dis. 1995 Dec;172(6):1630–1633. doi: 10.1093/infdis/172.6.1630. [DOI] [PubMed] [Google Scholar]
  28. Moore K. W., O'Garra A., de Waal Malefyt R., Vieira P., Mosmann T. R. Interleukin-10. Annu Rev Immunol. 1993;11:165–190. doi: 10.1146/annurev.iy.11.040193.001121. [DOI] [PubMed] [Google Scholar]
  29. More S. J., Copeman D. B. A highly specific and sensitive monoclonal antibody-based ELISA for the detection of circulating antigen in bancroftian filariasis. Trop Med Parasitol. 1990 Dec;41(4):403–406. [PubMed] [Google Scholar]
  30. Mosmann T. R., Coffman R. L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173. doi: 10.1146/annurev.iy.07.040189.001045. [DOI] [PubMed] [Google Scholar]
  31. Oothuman P., Denham D. A., McGreevy P. B., Nelson G. S., Rogers R. Successful vaccination of cats against Brugia pahangi with larvae attenuated by irradiation with 10 krad cobalt 60. Parasite Immunol. 1979 Autumn;1(3):209–216. doi: 10.1111/j.1365-3024.1979.tb00707.x. [DOI] [PubMed] [Google Scholar]
  32. Ottesen E. A. Immunological aspects of lymphatic filariasis and onchocerciasis in man. Trans R Soc Trop Med Hyg. 1984;78 (Suppl):9–18. doi: 10.1016/0035-9203(84)90309-2. [DOI] [PubMed] [Google Scholar]
  33. Ottesen E. A. The Wellcome Trust Lecture. Infection and disease in lymphatic filariasis: an immunological perspective. Parasitology. 1992;104 (Suppl):S71–S79. doi: 10.1017/s0031182000075259. [DOI] [PubMed] [Google Scholar]
  34. Ottesen E. A., Weller P. F., Heck L. Specific cellular immune unresponsiveness in human filariasis. Immunology. 1977 Sep;33(3):413–421. [PMC free article] [PubMed] [Google Scholar]
  35. Ottesen E. A., Weller P. F., Lunde M. N., Hussain R. Endemic filariasis on a Pacific Island. II. Immunologic aspects: immunoglobulin, complement, and specific antifilarial IgG, IgM, and IgE antibodies. Am J Trop Med Hyg. 1982 Sep;31(5):953–961. [PubMed] [Google Scholar]
  36. Piessens W. F., McGreevy P. B., Piessens P. W., McGreevy M., Koiman I., Saroso J. S., Dennis D. T. Immune responses in human infections with Brugia malayi: specific cellular unresponsiveness to filarial antigens. J Clin Invest. 1980 Jan;65(1):172–179. doi: 10.1172/JCI109648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Piessens W. F., McGreevy P. B., Ratiwayanto S., McGreevy M., Piessens P. W., Koiman I., Saroso J. S., Dennis D. T. Immune responses in human infections with Brugia malayi: correlation of cellular and humoral reactions to microfilarial antigens with clinical status. Am J Trop Med Hyg. 1980 Jul;29(4):563–570. doi: 10.4269/ajtmh.1980.29.563. [DOI] [PubMed] [Google Scholar]
  38. Sabbatini A. R., Werner P. A., Guha C., Paddock G. V., Galbraith R. M. The vitamin D-binding protein gene: quantitation of amplified nucleic acids by ELISA. Biotechniques. 1993 Oct;15(4):706–713. [PubMed] [Google Scholar]
  39. Sher A., Coffman R. L. Regulation of immunity to parasites by T cells and T cell-derived cytokines. Annu Rev Immunol. 1992;10:385–409. doi: 10.1146/annurev.iy.10.040192.002125. [DOI] [PubMed] [Google Scholar]
  40. Sher A., Fiorentino D., Caspar P., Pearce E., Mosmann T. Production of IL-10 by CD4+ T lymphocytes correlates with down-regulation of Th1 cytokine synthesis in helminth infection. J Immunol. 1991 Oct 15;147(8):2713–2716. [PubMed] [Google Scholar]
  41. Srividya A., Pani S. P., Rajagopalan P. K., Bundy D. A., Grenfell B. T. The dynamics of infection and disease in bancroftian filariasis. Trans R Soc Trop Med Hyg. 1991 Mar-Apr;85(2):255–259. doi: 10.1016/0035-9203(91)90046-2. [DOI] [PubMed] [Google Scholar]
  42. Steel C., Nutman T. B. Regulation of IL-5 in onchocerciasis. A critical role for IL-2. J Immunol. 1993 Jun 15;150(12):5511–5518. [PubMed] [Google Scholar]
  43. Weil G. J., Jain D. C., Santhanam S., Malhotra A., Kumar H., Sethumadhavan K. V., Liftis F., Ghosh T. K. A monoclonal antibody-based enzyme immunoassay for detecting parasite antigenemia in bancroftian filariasis. J Infect Dis. 1987 Aug;156(2):350–355. doi: 10.1093/infdis/156.2.350. [DOI] [PubMed] [Google Scholar]
  44. Yamamura M., Uyemura K., Deans R. J., Weinberg K., Rea T. H., Bloom B. R., Modlin R. L. Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science. 1991 Oct 11;254(5029):277–279. doi: 10.1126/science.254.5029.277. [DOI] [PubMed] [Google Scholar]
  45. Yates J. A., Higashi G. I. Brugia malayi: vaccination of jirds with 60cobalt-attenuated infective stage larvae protects against homologous challenge. Am J Trop Med Hyg. 1985 Nov;34(6):1132–1137. doi: 10.4269/ajtmh.1985.34.1132. [DOI] [PubMed] [Google Scholar]

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