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. 1989 Mar;57(3):951–956. doi: 10.1128/iai.57.3.951-956.1989

Reduced suppressor cell response to Mycobacterium leprae in lepromatous leprosy.

M D Sasiain 1, S de la Barrera 1, R Valdez 1, L M Balina 1
PMCID: PMC313204  PMID: 2521841

Abstract

We have previously shown that concanavalin A (ConA) induction of suppressor cell activity is impaired in patients with lepromatous leprosy (LL). In this study, we demonstrated that the proportion of cells bearing the Leu8 antigen (associated with suppressor-inducer cells) is low in LL patients and tends to normalize during the erythema nodosum leprosum (ENL) episode. Antigen-induced suppressor cell function was evaluated by a two-stage assay. In the first stage, peripheral blood mononuclear cells (PBMC) were cultured for 5 days either in the presence of gamma-irradiated Mycobacterium leprae or in tissue culture medium as a control. In the second stage, mitomycin C-treated suppressor or control cells were added to phytohemagglutinin (PHA)- or ConA-stimulated autologous PBMC. The results indicate that the ability of M. leprae to induce suppressor activity was lower in LL patients than in patients with tuberculoid (TT) and intermediate clinical (BB, BL, BT) forms and Mycobacterium bovis BCG-immunized normal controls. In ENL patients, the percent suppression was between that of TT and normal individuals. M. leprae-induced suppression was more effective on ConA- than on PHA-triggered T-cell proliferation in all groups. In contrast, normal PBMC cultured for 5 days in RPMI 1640 medium (N-C) and cells from patients with leprosy (TT-C and LL-C) had effects of their own on PHA- or ConA-induced proliferation. LL-C depressed the response to ConA and enhanced PHA-induced proliferation of autologous cells. Conversely, TT-C reduced PHA-induced proliferation and increased the ConA response. Suppression of proliferation could not be overcome with exogenous interleukin-2 and was not related to the induction of the Tac antigen. The abilities of LL, TT, ENL, and normal cells to proliferate upon PHA or ConA stimulus were similar, indicating that the defect in the generation of in vitro suppression by M. leprae in LL patients occurred during the induction period (step 1 of assay).

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Selected References

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  1. Artz R. P., Jacobson R. R., Bullock W. E. Decreased suppressor cell activity in disseminated granulomatous infections. Clin Exp Immunol. 1980 Aug;41(2):343–352. [PMC free article] [PubMed] [Google Scholar]
  2. Bjune G. In vitro lymphocyte stimulation in leprosy; simultaneous stimulation with Mycobacterium leprae antigens and phytohaemagglutinin. Clin Exp Immunol. 1979 Jun;36(3):479–487. [PMC free article] [PubMed] [Google Scholar]
  3. Bullock W. E., Watson S., Nelson K. E., Schauf V., Makonkawkeyoon S., Jacobson R. R. Aberrant immunoregulatory control of B lymphocyte function in lepromatous leprosy. Clin Exp Immunol. 1982 Jul;49(1):105–114. [PMC free article] [PubMed] [Google Scholar]
  4. Böyum A. A one-stage procedure for isolation of granulocytes and lymphocytes from human blood. General sedimentation properties of white blood cells in a 1g gravity field. Scand J Clin Lab Invest Suppl. 1968;97:51–76. [PubMed] [Google Scholar]
  5. Closs O., Reitan L. J., Negassi K., Harboe M., Belehu A. In vitro stimulation of lymphocytes in leprosy patients, healthy contacts of leprosy patients, and subjects not exposed to leprosy. Comparison of an antigen fraction prepared from Mycobacterium leprae and tuberculin-purified protein derivative. Scand J Immunol. 1982 Aug;16(2):103–115. doi: 10.1111/j.1365-3083.1982.tb00704.x. [DOI] [PubMed] [Google Scholar]
  6. Damle N. K., Childs A. L., Doyle L. V. Immunoregulatory T lymphocytes in man. Soluble antigen-specific suppressor-inducer T lymphocytes are derived from the CD4+CD45R-p80+ subpopulation. J Immunol. 1987 Sep 1;139(5):1501–1508. [PubMed] [Google Scholar]
  7. Damle N. K., Mohagheghpour N., Engleman E. G. Soluble antigen-primed inducer T cells activate antigen-specific suppressor T cells in the absence of antigen-pulsed accessory cells: phenotypic definition of suppressor-inducer and suppressor-effector cells. J Immunol. 1984 Feb;132(2):644–650. [PubMed] [Google Scholar]
  8. Faber W. R., Leiker D. L., Nengerman I. M., Zeijlemaker W. P., Schellekens P. T. Lymphocyte transformation test in leprosy: decreased lymphocyte reactivity to Mycobacterium leprae in lepromatous leprosy, with no evidence for a generalized impairment. Infect Immun. 1978 Dec;22(3):649–656. doi: 10.1128/iai.22.3.649-656.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Godal T., Myklestad B., Samuel D. R., Myrvang B. Characterization of the cellular immune defect in lepromatous leprosy: a specific lack of circulating Mycobacterium leprae-reactive lymphocytes. Clin Exp Immunol. 1971 Dec;9(6):821–831. [PMC free article] [PubMed] [Google Scholar]
  10. Kanof M. E., Strober W., James S. P. Induction of CD4 suppressor T cells with anti-Leu-8 antibody. J Immunol. 1987 Jul 1;139(1):49–54. [PubMed] [Google Scholar]
  11. Kansas G. S., Engleman E. G. Phenotypic identification of suppressor-effector, suppressor-amplifier and suppressor-inducer T cells of B cell differentiation in man. Eur J Immunol. 1987 Apr;17(4):453–457. doi: 10.1002/eji.1830170403. [DOI] [PubMed] [Google Scholar]
  12. Kansas G. S., Wood G. S., Fishwild D. M., Engleman E. G. Functional characterization of human T lymphocyte subsets distinguished by monoclonal anti-leu-8. J Immunol. 1985 May;134(5):2995–3002. [PubMed] [Google Scholar]
  13. Kaplan G., Gandhi R. R., Weinstein D. E., Levis W. R., Patarroyo M. E., Brennan P. J., Cohn Z. A. Mycobacterium leprae antigen-induced suppression of T cell proliferation in vitro. J Immunol. 1987 May 1;138(9):3028–3034. [PubMed] [Google Scholar]
  14. Kaplan G., Weinstein D. E., Steinman R. M., Levis W. R., Elvers U., Patarroyo M. E., Cohn Z. A. An analysis of in vitro T cell responsiveness in lepromatous leprosy. J Exp Med. 1985 Sep 1;162(3):917–929. doi: 10.1084/jem.162.3.917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mehra V., Brennan P. J., Rada E., Convit J., Bloom B. R. Lymphocyte suppression in leprosy induced by unique M. leprae glycolipid. Nature. 1984 Mar 8;308(5955):194–196. doi: 10.1038/308194a0. [DOI] [PubMed] [Google Scholar]
  16. Mehra V., Mason L. H., Fields J. P., Bloom B. R. Lepromin-induced suppressor cells in patients with leprosy. J Immunol. 1979 Oct;123(4):1813–1817. [PubMed] [Google Scholar]
  17. 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]
  18. Modlin R. L., Mehra V., Wong L., Fujimiya Y., Chang W. C., Horwitz D. A., Bloom B. R., Rea T. H., Pattengale P. K. Suppressor T lymphocytes from lepromatous leprosy skin lesions. J Immunol. 1986 Nov 1;137(9):2831–2834. [PubMed] [Google Scholar]
  19. Modlin R. L., Melancon-Kaplan J., Young S. M., Pirmez C., Kino H., Convit J., Rea T. H., Bloom B. R. Learning from lesions: patterns of tissue inflammation in leprosy. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1213–1217. doi: 10.1073/pnas.85.4.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Moore K., Nesbitt A. M. Identification and isolation of OKT4+ suppressor cells with the monoclonal antibody WR16. Immunology. 1986 Aug;58(4):659–664. [PMC free article] [PubMed] [Google Scholar]
  21. Mustafa A. S., Godal T. In vitro induction of human suppressor T cells by mycobacterial antigens. BCG activated OKT4+ cells mediate suppression of antigen induced T cell proliferation. Clin Exp Immunol. 1983 Apr;52(1):29–37. [PMC free article] [PubMed] [Google Scholar]
  22. Möller G. Concanavalin-A-activated lymphocytes suppress immune responses in vitro but are helper cells in vivo. Scand J Immunol. 1985 Jan;21(1):31–34. doi: 10.1111/j.1365-3083.1985.tb01399.x. [DOI] [PubMed] [Google Scholar]
  23. Nath I., Singh R. The suppressive effect of M. leprae on the in vitro proliferative responses of lymphocytes from patients with leprosy. Clin Exp Immunol. 1980 Sep;41(3):406–414. [PMC free article] [PubMed] [Google Scholar]
  24. Ottenhoff T. H., Elferink D. G., Klatser P. R., de Vries R. R. Cloned suppressor T cells from a lepromatous leprosy patient suppress Mycobacterium leprae reactive helper T cells. 1986 Jul 31-Aug 6Nature. 322(6078):462–464. doi: 10.1038/322462a0. [DOI] [PubMed] [Google Scholar]
  25. Palacios R., Möller G. T cell growth factor abrogates concanavalin A-induced suppressor cell function. J Exp Med. 1981 May 1;153(5):1360–1365. doi: 10.1084/jem.153.5.1360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Reinherz E. L., Morimoto C., Fitzgerald K. A., Hussey R. E., Daley J. F., Schlossman S. F. Heterogeneity of human T4+ inducer T cells defined by a monoclonal antibody that delineates two functional subpopulations. J Immunol. 1982 Jan;128(1):463–468. [PubMed] [Google Scholar]
  27. 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]
  28. Sasiain M. C., Ruibal Ares B., Baliña L. M., Valdez R., Bachmann A. E. ConA-induced suppressor cells in lepromatous leprosy patients during and after erythema nodosum leprosum. Int J Lepr Other Mycobact Dis. 1983 Sep;51(3):321–327. [PubMed] [Google Scholar]
  29. Serra H. M., Krowka J. F., Ledbetter J. A., Pilarski L. M. Loss of CD45R (Lp220) represents a post-thymic T cell differentiation event. J Immunol. 1988 Mar 1;140(5):1435–1441. [PubMed] [Google Scholar]
  30. Stoner G. L., Atlaw T., Touw J., Belehu A. Antigen-specific suppressor cells in subclinical leprosy infection. Lancet. 1981 Dec 19;2(8260-61):1372–1377. doi: 10.1016/s0140-6736(81)92798-7. [DOI] [PubMed] [Google Scholar]
  31. Takeuchi T., Rudd C. E., Schlossman S. F., Morimoto C. Induction of suppression following autologous mixed lymphocyte reaction; role of a novel 2H4 antigen. Eur J Immunol. 1987 Jan;17(1):97–103. doi: 10.1002/eji.1830170117. [DOI] [PubMed] [Google Scholar]
  32. Thomas Y., Rogozinski L., Irigoyen O. H., Friedman S. M., Kung P. C., Goldstein G., Chess L. Functional analysis of human T cell subsets defined by monoclonal antibodies. IV. Induction of suppressor cells within the OKT4+ population. J Exp Med. 1981 Aug 1;154(2):459–467. doi: 10.1084/jem.154.2.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Thomas Y., Rogozinski L., Irigoyen O. H., Shen H. H., Talle M. A., Goldstein G., Chess L. Functional analysis of human T cell subsets defined by monoclonal antibodies. V. Suppressor cells within the activated OKT4+ population belong to a distinct subset. J Immunol. 1982 Mar;128(3):1386–1390. [PubMed] [Google Scholar]
  34. Touw J., Stoner G. L., Belehu A. Effect of Mycobacterium leprae on lymphocyte proliferation: suppression of mitogen and antigen responses of human peripheral blood mononuclear cells. Clin Exp Immunol. 1980 Sep;41(3):397–405. [PMC free article] [PubMed] [Google Scholar]
  35. Waldmann T. A. The structure, function, and expression of interleukin-2 receptors on normal and malignant lymphocytes. Science. 1986 May 9;232(4751):727–732. doi: 10.1126/science.3008337. [DOI] [PubMed] [Google Scholar]
  36. del Carmen Sasiain M., de la Barrera S., Ruibal-Ares B., Cardama J. E., Gatti J. C., de Bracco M. M. Suppressor response in lepromatous leprosy patients: role of Leu 2a cells. Immunology. 1987 Jan;60(1):13–18. [PMC free article] [PubMed] [Google Scholar]

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