Abstract
Dendritic cell (DC)-enriched cell populations from anergic lepromatous leprosy (LL) patients were found to be several-hundred-fold more efficient than monocytes (MO) in promoting antigen-induced T cell responses in autologous accessory + T cell cultures. Whereas, the use of autologous monocytes over a wide concentration range failed to stimulate Mycobacterium leprae-induced T cell proliferation, DC at concentrations as low as 0.1% induced significant proliferation in 9/15 and interferon gamma production in 14/15 LL patients. Four of the LL patients who failed to show proliferation were, however, able to secrete interferon gamma in the same T cell + DC co-cultures. DC were able to present particulate leprae antigens to autologous T cells. This preference for DC as an accessory cell was not shown when the cross-reacting antigen PPD was used in parallel co-cultures. Though tuberculoid leprosy patients showed some improvement in T cell proliferation with DC as compared to MO constituted co-cultures, this was not statistically significant. These results suggest that there is a heterogeneity in accessory cell requirement across the leprosy spectrum and that many lepromatous patients possess M. leprae-reactive functional T cells.
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Selected References
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- Barnass S., Mace J., Steele J., Torres P., Gervasoni B., Ravioli R., Terencio J., Rook G. A., Waters M. F. Prevalence and specificity of the enhancing effect of three types of interleukin 2 on T cell responsiveness in 97 lepromatous leprosy patients of mixed ethnic origin. Clin Exp Immunol. 1986 Apr;64(1):41–49. [PMC free article] [PubMed] [Google Scholar]
- Birdi T. J., Mistry N. F., Mahadevan P. R., Antia N. H. Alterations in the membrane of macrophages from leprosy patients. Infect Immun. 1983 Jul;41(1):121–127. doi: 10.1128/iai.41.1.121-127.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Crow M. K., Kunkel H. G. Human dendritic cells: major stimulators of the autologous and allogeneic mixed leucocyte reactions. Clin Exp Immunol. 1982 Aug;49(2):338–346. [PMC free article] [PubMed] [Google Scholar]
- Gupta S., Curtis J., Turk J. L. Accessory cell function of cells of the mononuclear phagocyte system isolated from mycobacterial granulomas. Cell Immunol. 1985 Apr 1;91(2):425–433. doi: 10.1016/0008-8749(85)90240-0. [DOI] [PubMed] [Google Scholar]
- Haregewoin A., Godal T., Mustafa A. S., Belehu A., Yemaneberhan T. T-cell conditioned media reverse T-cell unresponsiveness in lepromatous leprosy. Nature. 1983 May 26;303(5915):342–344. doi: 10.1038/303342a0. [DOI] [PubMed] [Google Scholar]
- Inaba K., Koide S., Steinman R. M. Properties of memory T lymphocytes isolated from the mixed leukocyte reaction. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7686–7690. doi: 10.1073/pnas.82.22.7686. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inaba K., Steinman R. M. Resting and sensitized T lymphocytes exhibit distinct stimulatory (antigen-presenting cell) requirements for growth and lymphokine release. J Exp Med. 1984 Dec 1;160(6):1717–1735. doi: 10.1084/jem.160.6.1717. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaye P. M., Chain B. M., Feldmann M. Nonphagocytic dendritic cells are effective accessory cells for anti-mycobacterial responses in vitro. J Immunol. 1985 Mar;134(3):1930–1934. [PubMed] [Google Scholar]
- Laal S., Bhutani L. K., Nath I. Natural emergence of antigen-reactive T cells in lepromatous leprosy patients during erythema nodosum leprosum. Infect Immun. 1985 Dec;50(3):887–892. doi: 10.1128/iai.50.3.887-892.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mehra V., Mason L. H., Rothman W., Reinherz E., Schlossman S. F., Bloom B. R. Delineation of a human T cell subset responsible for lepromin-induced suppression in leprosy patients. J Immunol. 1980 Sep;125(3):1183–1188. [PubMed] [Google Scholar]
- Mittal A., Nath I. Human T cell proliferative responses to particulate microbial antigens are supported by populations enriched in dendritic cells. Clin Exp Immunol. 1987 Sep;69(3):611–617. [PMC free article] [PubMed] [Google Scholar]
- Modlin R. L., Gebhard J. F., Taylor C. R., Rea T. H. In situ characterization of T lymphocyte subsets in the reactional states of leprosy. Clin Exp Immunol. 1983 Jul;53(1):17–24. [PMC free article] [PubMed] [Google Scholar]
- Mohagheghpour N., Gelber R. H., Larrick J. W., Sasaki D. T., Brennan P. J., Engleman E. G. Defective cell-mediated immunity in leprosy: failure of T cells from lepromatous leprosy patients to respond to Mycobacterium leprae is associated with defective expression of interleukin 2 receptors and is not reconstituted by interleukin 2. J Immunol. 1985 Aug;135(2):1443–1449. [PubMed] [Google Scholar]
- Montreewasuwat N., Curtis J., Turk J. L. Accessory cell function of cells isolated from Mycobacterium leprae-induced granulomas. Cell Immunol. 1986 Oct 15;102(2):346–354. doi: 10.1016/0008-8749(86)90428-4. [DOI] [PubMed] [Google Scholar]
- Narayanan R. B., Laal S., Sharma A. K., Bhutani L. K., Nath I. Differences in predominant T cell phenotypes and distribution pattern in reactional lesions of tuberculoid and lepromatous leprosy. Clin Exp Immunol. 1984 Mar;55(3):623–628. [PMC free article] [PubMed] [Google Scholar]
- Nath I., Jayaraman J., Sathish M., Bhutani L. K., Sharma A. K. Inhibition of interleukin-2 production by adherent cell factors from lepromatous leprosy patients. Clin Exp Immunol. 1984 Dec;58(3):531–538. [PMC free article] [PubMed] [Google Scholar]
- Nathan C. F., Murray H. W., Wiebe M. E., Rubin B. Y. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med. 1983 Sep 1;158(3):670–689. doi: 10.1084/jem.158.3.670. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nogueira N., Kaplan G., Levy E., Sarno E. N., Kushner P., Granelli-Piperno A., Vieira L., Colomer Gould V., Levis W., Steinman R. Defective gamma interferon production in leprosy. Reversal with antigen and interleukin 2. J Exp Med. 1983 Dec 1;158(6):2165–2170. doi: 10.1084/jem.158.6.2165. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Prasad H. K., Nath I. Incorporation of 3H-thymidine in Mycobacterium leprae within differentiated human macrophages. J Med Microbiol. 1981 Aug;14(3):279–293. doi: 10.1099/00222615-14-3-279. [DOI] [PubMed] [Google Scholar]
- Ridley D. S., Jopling W. H. Classification of leprosy according to immunity. A five-group system. Int J Lepr Other Mycobact Dis. 1966 Jul-Sep;34(3):255–273. [PubMed] [Google Scholar]
- Sathish M., Bhutani L. K., Sharma A. K., Nath I. Monocyte-derived soluble suppressor factor(s) in patients with lepromatous leprosy. Infect Immun. 1983 Dec;42(3):890–899. doi: 10.1128/iai.42.3.890-899.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Steinman R. M., Cohn Z. A. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med. 1973 May 1;137(5):1142–1162. doi: 10.1084/jem.137.5.1142. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thangaraj H., Laal S., Thangaraj I., Nath I. Epidermal changes in reactional leprosy: keratinocyte Ia expression as an indicator of cell-mediated immune responses. Int J Lepr Other Mycobact Dis. 1988 Sep;56(3):401–407. [PubMed] [Google Scholar]
- Unanue E. R. The regulation of lymphocyte functions by the macrophage. Immunol Rev. 1978;40:227–255. doi: 10.1111/j.1600-065x.1978.tb00408.x. [DOI] [PubMed] [Google Scholar]
- Van Voorhis W. C., Hair L. S., Steinman R. M., Kaplan G. Human dendritic cells. Enrichment and characterization from peripheral blood. J Exp Med. 1982 Apr 1;155(4):1172–1187. doi: 10.1084/jem.155.4.1172. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yam L. T., Li C. Y., Crosby W. H. Cytochemical identification of monocytes and granulocytes. Am J Clin Pathol. 1971 Mar;55(3):283–290. doi: 10.1093/ajcp/55.3.283. [DOI] [PubMed] [Google Scholar]