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Home / Equine Research Bank / Vet Immunol Immunopathol / Early development of cytotoxic T lymphocytes in neonatal foa...
Veterinary immunology and immunopathology2011; 141(3-4); 312-316; doi: 10.1016/j.vetimm.2011.03.015

Early development of cytotoxic T lymphocytes in neonatal foals following oral inoculation with Rhodococcus equi.

Abstract: Rhodococcus equi is an important respiratory pathogen of young foals for which a vaccine has long been sought. Two major impediments to effective vaccination are the functionally immature type I immune responses of neonatal foals and early exposure to the bacterium via the environment. Despite these obstacles, it appears that under specific circumstances foals can develop a protective immune response. In this study we investigated the protective mechanisms behind oral inoculation of foals with virulent R. equi bacteria. Two foals receiving an oral inoculum demonstrated accelerated development of R. equi specific cytotoxic T lymphocytes (CTL) as evidenced by significant lysis of R. equi infected, ELA-A mismatched cells at 3 weeks of age. As in a previous study, CTL were not detected until 5-6 weeks of age in two control foals. At each time point the ability of foal peripheral blood mononuclear cells (PBMC) to produce IFN-γ following stimulation with live R. equi or extracted cell wall lipids was similar to that of an adult horse control and between foals, regardless of treatment. These results provide a potential mechanism of protection which has previously been shown to occur following oral inoculation, and suggest that the early detection of CTL may be a useful marker for induction of protective immunity.
Copyright © 2011 Elsevier B.V. All rights reserved.
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Publication Date: 2011-03-21 PubMed ID: 21481947PubMed Central: PMC3345954DOI: 10.1016/j.vetimm.2011.03.015Google Scholar: Lookup
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article focuses on investigation and observation of an accelerated immune response in newborn foals when orally inoculated with virulent R. equi bacteria. The study tracked the development of specific cytotoxic T lymphocytes and results suggest that the early detection of these cells may be indicative of a protective immune response.

Research Purpose and Challenges

  • The research is centered around Rhodococcus equi, a prominent respiratory pathogen in young foals and the attempts to create a vaccine against it. The pathogen is typically acquired through early environmental exposure.
  • There are two main issues with vaccinating foals against R. equi. Firstly, newborn foals do not exhibit strong Type I immune responses. Secondly, foals are often exposed to the bacterium early in their lives via their surroundings.
  • In spite of these issues, the researchers noticed that under certain conditions, foals can build a protective immune response.

Research Methodology

  • The study involved orally administering a dose of R. equi bacteria to two foals. The researchers then monitored the development of R. equi-specific cytotoxic T lymphocytes (CTLs) – immune cells that directly kill target cells infected by the bacteria.
  • Two foals which received the bacteria showed an earlier development of CTLs, showing substantial lysis (or killing) of R. equi-infected cells at three weeks of age. In comparison, a previous study noted cytotoxic T lymphocytes were usually not detected until 5-6 weeks in control foals that didn’t receive the oral inoculant.

Results and Inferences

  • Meanwhile, the production of an immunoregulatory protein called IFN-γ by the foals’ peripheral blood mononuclear cells (PBMCs), when stimulated with live R. equi or cell wall lipids extracted from it, was as responsive as that of an adult horse and consistent amongst treated and untreated foals.
  • The findings from this experiment suggest that R. equi oral inoculation may be fostering a quicker immune response, highlighted by the early surge of cytotoxic T lymphocytes.
  • More than just a defensive mechanism, the early appearance of CTLs might be a good sign of the initiation of protective immunity.

Cite This Article

APA
Harris SP, Hines MT, Mealey RH, Alperin DC, Hines SA. (2011). Early development of cytotoxic T lymphocytes in neonatal foals following oral inoculation with Rhodococcus equi. Vet Immunol Immunopathol, 141(3-4), 312-316. https://doi.org/10.1016/j.vetimm.2011.03.015

Publication

Veterinary immunology and immunopathology
ISSN: 1873-2534
NlmUniqueID: 8002006
Country: Netherlands
Language: English
Volume: 141
Issue: 3-4
Pages: 312-316

Researcher Affiliations

Harris, Seth P
  • Department of Veterinary Microbiology and Pathology, Washington State University, College of Veterinary Medicine, PO Box 647040, Pullman, WA 99164-7040, USA.
Hines, Melissa T
    Mealey, Robert H
      Alperin, Debra C
        Hines, Stephen A

          MeSH Terms

          • Actinomycetales Infections / immunology
          • Actinomycetales Infections / microbiology
          • Actinomycetales Infections / veterinary
          • Aging
          • Animals
          • Animals, Newborn
          • Disease Susceptibility
          • Horse Diseases / immunology
          • Horse Diseases / microbiology
          • Horses
          • Rhodococcus equi
          • T-Lymphocytes, Cytotoxic / physiology

          Grant Funding

          • T32 AI007025 / NIAID NIH HHS
          • T32 AI007025-24 / NIAID NIH HHS

          Conflict of Interest Statement

          There are no conflicts of interest.

          References

          This article includes 30 references
          1. Adkins B, Leclerc C, Marshall-Clarke S. Neonatal adaptive immunity comes of age.. Nat Rev Immunol 2004 Jul;4(7):553-64.
            pubmed: 15229474doi: 10.1038/nri1394google scholar: lookup
          2. Barral DC, Brenner MB. CD1 antigen presentation: how it works.. Nat Rev Immunol 2007 Dec;7(12):929-41.
            pubmed: 18037897doi: 10.1038/nri2191google scholar: lookup
          3. Björkstén B. The intrauterine and postnatal environments.. J Allergy Clin Immunol 1999 Dec;104(6):1119-27.
            pubmed: 10588990doi: 10.1016/s0091-6749(99)70002-3google scholar: lookup
          4. Boyd NK, Cohen ND, Lim WS, Martens RJ, Chaffin MK, Ball JM. Temporal changes in cytokine expression of foals during the first month of life.. Vet Immunol Immunopathol 2003 Mar 20;92(1-2):75-85.
            pubmed: 12628765doi: 10.1016/s0165-2427(03)00021-7google scholar: lookup
          5. Breathnach CC, Sturgill-Wright T, Stiltner JL, Adams AA, Lunn DP, Horohov DW. Foals are interferon gamma-deficient at birth.. Vet Immunol Immunopathol 2006 Aug 15;112(3-4):199-209.
            pubmed: 16621024doi: 10.1016/j.vetimm.2006.02.010google scholar: lookup
          6. Buntain S, Carter C, Kuskie K, Smith J, Stepusin R, Chaffin MK, Takai S, Cohen N. Frequency of Rhodococcus equi in Feces of Mares in Central Kentucky. Journal of Equine Veterinary Science 2010;30:191–195.
          7. Chaffin MK, Cohen ND, Martens RJ, Edwards RF, Nevill M. Foal-related risk factors associated with development of Rhodococcus equi pneumonia on farms with endemic infection.. J Am Vet Med Assoc 2003 Dec 15;223(12):1791-9.
            pubmed: 14690209doi: 10.2460/javma.2003.223.1791google scholar: lookup
          8. Chang SR, Wang KJ, Lu YF, Yang LJ, Chen WJ, Lin YH, Chang HH, Wang SL. Characterization of early gamma interferon (IFN-gamma) expression during murine listeriosis: identification of NK1.1+ CD11c+ cells as the primary IFN-gamma-expressing cells.. Infect Immun 2007 Mar;75(3):1167-76.
            pmc: PMC1828594pubmed: 17158904doi: 10.1128/iai.01026-06google scholar: lookup
          9. Chirino-Trejo JM, Prescott JF, Yager JA. Protection of foals against experimental Rhodococcus equi pneumonia by oral immunization.. Can J Vet Res 1987 Oct;51(4):444-7.
            pmc: PMC1255362pubmed: 3453264
          10. Cohen ND, Carter CN, Scott HM, Chaffin MK, Smith JL, Grimm MB, Kuskie KR, Takai S, Martens RJ. Association of soil concentrations of Rhodococcus equi and incidence of pneumonia attributable to Rhodococcus equi in foals on farms in central Kentucky.. Am J Vet Res 2008 Mar;69(3):385-95.
            pubmed: 18312138doi: 10.2460/ajvr.69.3.385google scholar: lookup
          11. Darrah PA, Monaco MC, Jain S, Hondalus MK, Golenbock DT, Mosser DM. Innate immune responses to Rhodococcus equi.. J Immunol 2004 Aug 1;173(3):1914-24.
            pubmed: 15265925doi: 10.4049/jimmunol.173.3.1914google scholar: lookup
          12. Eger KA, Sundrud MS, Motsinger AA, Tseng M, Van Kaer L, Unutmaz D. Human natural killer T cells are heterogeneous in their capacity to reprogram their effector functions.. PLoS One 2006 Dec 20;1(1):e50.
            pmc: PMC1762372pubmed: 17183680doi: 10.1371/journal.pone.0000050google scholar: lookup
          13. Gibbons DL, Haque SF, Silberzahn T, Hamilton K, Langford C, Ellis P, Carr R, Hayday AC. Neonates harbour highly active gammadelta T cells with selective impairments in preterm infants.. Eur J Immunol 2009 Jul;39(7):1794-806.
            pubmed: 19544311doi: 10.1002/eji.200939222google scholar: lookup
          14. Harris SP, Fujiwara N, Mealey RH, Alperin DC, Naka T, Goda R, Hines SA. Identification of Rhodococcus equi lipids recognized by host cytotoxic T lymphocytes.. Microbiology (Reading) 2010 Jun;156(Pt 6):1836-1847.
            pmc: PMC4086205pubmed: 20299405doi: 10.1099/mic.0.035915-0google scholar: lookup
          15. Hines MT, Paasch KM, Alperin DC, Palmer GH, Westhoff NC, Hines SA. Immunity to Rhodococcus equi: antigen-specific recall responses in the lungs of adult horses.. Vet Immunol Immunopathol 2001 May 10;79(1-2):101-14.
            pubmed: 11356253doi: 10.1016/s0165-2427(01)00258-6google scholar: lookup
          16. Hines SA, Stone DM, Hines MT, Alperin DC, Knowles DP, Norton LK, Hamilton MJ, Davis WC, McGuire TC. Clearance of virulent but not avirulent Rhodococcus equi from the lungs of adult horses is associated with intracytoplasmic gamma interferon production by CD4+ and CD8+ T lymphocytes.. Clin Diagn Lab Immunol 2003 Mar;10(2):208-15.
            pmc: PMC150533pubmed: 12626444doi: 10.1128/cdli.10.2.208-215.2003google scholar: lookup
          17. Hondalus MK. Pathogenesis and virulence of Rhodococcus equi.. Vet Microbiol 1997 Jun 16;56(3-4):257-68.
            pubmed: 9226840doi: 10.1016/s0378-1135(97)00094-1google scholar: lookup
          18. Hooper-McGrevy KE, Wilkie BN, Prescott JF. Virulence-associated protein-specific serum immunoglobulin G-isotype expression in young foals protected against Rhodococcus equi pneumonia by oral immunization with virulent R. equi.. Vaccine 2005 Dec 30;23(50):5760-7.
            pubmed: 16112256doi: 10.1016/j.vaccine.2005.07.050google scholar: lookup
          19. Iwasaki A. Mucosal dendritic cells.. Annu Rev Immunol 2007;25:381-418.
            pubmed: 17378762doi: 10.1146/annurev.immunol.25.022106.141634google scholar: lookup
          20. Jacks S, Giguère S, Crawford PC, Castleman WL. Experimental infection of neonatal foals with Rhodococcus equi triggers adult-like gamma interferon induction.. Clin Vaccine Immunol 2007 Jun;14(6):669-77.
            pmc: PMC1951072pubmed: 17409222doi: 10.1128/cvi.00042-07google scholar: lookup
          21. Kanaly ST, Hines SA, Palmer GH. Failure of pulmonary clearance of Rhodococcus equi infection in CD4+ T-lymphocyte-deficient transgenic mice.. Infect Immun 1993 Nov;61(11):4929-32.
            pmc: PMC281259pubmed: 8104903doi: 10.1128/iai.61.11.4929-4932.1993google scholar: lookup
          22. Kanaly ST, Hines SA, Palmer GH. Transfer of a CD4+ Th1 cell line to nude mice effects clearance of Rhodococcus equi from the lung.. Infect Immun 1996 Apr;64(4):1126-32.
            pmc: PMC173893pubmed: 8606068doi: 10.1128/iai.64.4.1126-1132.1996google scholar: lookup
          23. Liu T, Nerren J, Liu M, Martens R, Cohen N. Basal and stimulus-induced cytokine expression is selectively impaired in peripheral blood mononuclear cells of newborn foals.. Vaccine 2009 Jan 29;27(5):674-83.
            pubmed: 19056444doi: 10.1016/j.vaccine.2008.11.040google scholar: lookup
          24. Lopez AM, Hines MT, Palmer GH, Alperin DC, Hines SA. Identification of pulmonary T-lymphocyte and serum antibody isotype responses associated with protection against Rhodococcus equi.. Clin Diagn Lab Immunol 2002 Nov;9(6):1270-6.
            pmc: PMC130094pubmed: 12414760doi: 10.1128/cdli.9.6.1270-1276.2002google scholar: lookup
          25. McGuire TC, Tumas DB, Byrne KM, Hines MT, Leib SR, Brassfield AL, O'Rourke KI, Perryman LE. Major histocompatibility complex-restricted CD8+ cytotoxic T lymphocytes from horses with equine infectious anemia virus recognize Env and Gag/PR proteins.. J Virol 1994 Mar;68(3):1459-67.
            pmc: PMC236601pubmed: 8107209doi: 10.1128/jvi.68.3.1459-1467.1994google scholar: lookup
          26. Patton KM, McGuire TC, Fraser DG, Hines SA. Rhodococcus equi-infected macrophages are recognized and killed by CD8+ T lymphocytes in a major histocompatibility complex class I-unrestricted fashion.. Infect Immun 2004 Dec;72(12):7073-83.
            pmc: PMC529141pubmed: 15557631doi: 10.1128/iai.72.12.7073-7083.2004google scholar: lookup
          27. Patton KM, McGuire TC, Hines MT, Mealey RH, Hines SA. Rhodococcus equi-specific cytotoxic T lymphocytes in immune horses and development in asymptomatic foals.. Infect Immun 2005 Apr;73(4):2083-93.
            pmc: PMC1087435pubmed: 15784549doi: 10.1128/iai.73.4.2083-2093.2005google scholar: lookup
          28. Raghupathy R. Pregnancy: success and failure within the Th1/Th2/Th3 paradigm.. Semin Immunol 2001 Aug;13(4):219-27.
            pubmed: 11437629doi: 10.1006/smim.2001.0316google scholar: lookup
          29. Takai S. Epidemiology of Rhodococcus equi infections: a review.. Vet Microbiol 1997 Jun 16;56(3-4):167-76.
            pubmed: 9226831doi: 10.1016/s0378-1135(97)00085-0google scholar: lookup
          30. Watkins ML, Semple PL, Abel B, Hanekom WA, Kaplan G, Ress SR. Exposure of cord blood to Mycobacterium bovis BCG induces an innate response but not a T-cell cytokine response.. Clin Vaccine Immunol 2008 Nov;15(11):1666-73.
            pmc: PMC2583525pubmed: 18815231doi: 10.1128/cvi.00202-08google scholar: lookup

          Citations

          This article has been cited 7 times.
          1. Tallmadge RL, Wang M, Sun Q, Felippe MJB. Transcriptome analysis of immune genes in peripheral blood mononuclear cells of young foals and adult horses. PLoS One 2018;13(9):e0202646.
            doi: 10.1371/journal.pone.0202646pubmed: 30183726google scholar: lookup
          2. Giles C, Ndi O, Barton MD, Vanniasinkam T. An Adenoviral Vector Based Vaccine for Rhodococcus equi. PLoS One 2016;11(3):e0152149.
            doi: 10.1371/journal.pone.0152149pubmed: 27008624google scholar: lookup
          3. Buchanan RM, Mertins S, Wilson HL. Oral antigen exposure in extreme early life in lambs influences the magnitude of the immune response which can be generated in later life. BMC Vet Res 2013 Aug 12;9:160.
            doi: 10.1186/1746-6148-9-160pubmed: 23937675google scholar: lookup
          4. Buchanan RM, Tetland S, Wilson HL. Low dose antigen exposure for a finite period in newborn rats prevents induction of mucosal tolerance. PLoS One 2012;7(12):e51437.
            doi: 10.1371/journal.pone.0051437pubmed: 23251533google scholar: lookup
          5. Berghaus LJ, Venner M, Helbig H, Hildebrandt D, Hart K. The potential value of cytokine, cortisol and vitamin D profiles in foals from birth to weaning for respiratory disease prediction on a farm endemic for Rhodococcus equi pneumonia. Equine Vet J 2026 Mar;58(2):359-371.
            doi: 10.1111/evj.70093pubmed: 40923138google scholar: lookup
          6. da Silveira BP, Kahn SK, Legere RM, Bray JM, Cole-Pfeiffer HM, Golding MC, Cohen ND, Bordin AI. Enteral immunization with live bacteria reprograms innate immune cells and protects neonatal foals from pneumonia. Sci Rep 2025 May 25;15(1):18156.
            doi: 10.1038/s41598-025-02060-5pubmed: 40415003google scholar: lookup
          7. Mizuguchi Y, Tsuzuki N, Ebana MD, Suzuki Y, Kakuda T. IgG Subtype Response against Virulence-Associated Protein A in Foals Naturally Infected with Rhodococcus equi. Vet Sci 2024 Sep 9;11(9).
            doi: 10.3390/vetsci11090422pubmed: 39330801google scholar: lookup
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