Skip to main content
PMC home page
Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 1991 May;34(3):205–210. doi: 10.1007/BF01742314

Impairment in proliferation, lymphokine production and frequency distribution of mitogen-responsive and interleukin-2-producing cells in Hodgkin's disease

Rajendra N Damle 1, Suresh H Advani 2, Sudha G Gangal 1,✉
PMCID: PMC11037982  PMID: 1756538

Abstract

In this paper, we have correlated the ability of peripheral blood lymphocytes (PBL) from Hodgkin's Disease patients to proliferate in response to a mitogen, phytohaemagglutinin (PHA), with production of lymphokines interleukin-2 (IL-2) and interferon γ (IFNγ), accumulating in the activated lymphocyte culture supernatants. We have also studied the frequency distribution of PHA-responsive and IL-2-producing T cells from PBL using limiting-dilution analysis. We observed that the levels of IL-2 and IFNγ in the supernatants of activated lymphocytes from patients with Hodgkin's disease were significantly reduced compared to those of healthy donors. Substage-B patients showed marked reduction in the ability to produce IFNγ. Levels of IL-2 and IFNγ in the culture supernatants of PBL from Hodgkin's disease patients correlated positively with proliferative responses, when analysed by linear regressison (r = 0.79 andr = 0.60 respectively). However, production of the two lymphokines by activated lymphocytes from the same patients did not correlate (r = +0.04). Further, the frequencies of PHA-responsive cells and IL-2-producing cells in the PBL of patients with Hodgkin's disease (ranges 1/111–1/554 and 1/3009–1/6709 respectively) were also less than those of the healthy donors (ranges 1/80–1/181 and 1/761–1/1828 respectively). Proliferation, IL-2 production in bulk cultures and frequencies of PHA-responsive and IL-2-producing cells correlated well in individual healthy donors. Whereas, one patient (BC 11 214) with a frequency of PHA-responsive cells within normal limits had a very low frequency of IL-2-producing cells. Taken together, the results indicate abnormalities in cytokine production and frequency distribution of cells required for amplification of immune response in patients with Hodgkin's disease.

Key words: Hodgkin's disease, T cell hyporesponsiveness, Lymphokines, Limiting-dilution analysis

References

  • 1.Bergmann L, Mitrou PS, Demmer-Dieckmann F, Ruhmann FT, Weidmann E. Impaired T and B-cell functions in patients with Hodgkin's disease. Cancer Immunol Immunother. 1987;25:59. doi: 10.1007/BF00199302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Borden EC, Leonhardt PH. A quantitative semimicro, semiautomated colorimetric assay for interferon. J Lab Clin Med. 1977;89:1036. [PubMed] [Google Scholar]
  • 3.Boyum A. Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest. 1968;21([Suppl] 97):77. [PubMed] [Google Scholar]
  • 4.Damle RN, Tatake RJ, Advani SH, Gangal SG. Affinity of IL-2 receptors in relation to proliferation of mitogen activated lymphocytes in Hodgkin's disease. Br J Cancer. 1990;61:404. doi: 10.1038/bjc.1990.88. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Farrar WL, Ferris DK, Harel-Bellan A. The molecular basis of immune cytokine action. CRC Crit Rev Ther Drug Carrier Syst. 1989;5:229. [PubMed] [Google Scholar]
  • 6.Fisher RI. Implication of persistent T cell abnormalities for the etiology of Hodgkin's disease. Cancer Treat Rep. 1982;66:681. [PubMed] [Google Scholar]
  • 7.Fisher H, Hedlund G, Kalland T, Sjogren HO, Dohlsten M. Independent regulation of IFNγ and tumor necrosis factor by IL-1 in human T helper cells. J Immunol. 1990;145:3767. [PubMed] [Google Scholar]
  • 8.Ford RJ, Tsao T, Kouttab NM, Sahasrabuddhe CG, Mehta SR. Association of an interleukin abnormality with the T cell defect in Hodgkin's disease. Blood. 1984;64:386. [PubMed] [Google Scholar]
  • 9.Frasca D, Adorini L, Landolfo S, Doria G. Enhancing effect of IFN-gamma on helper T cell activity and IL-2 production. J Immunol. 1985;134:3907. [PubMed] [Google Scholar]
  • 10.Friedman RM, Vogel SN. Interferons with special emphasis on the immune system. Adv Immunol. 1983;34:97. doi: 10.1016/s0065-2776(08)60378-8. [DOI] [PubMed] [Google Scholar]
  • 11.Fujita T, Shibuya H, Ohashi T, Yamanishi K, Taniguchi T. Regulation of human interleukin-2 gene functional DNA sequences in the 5′ flanking region for the gene expression in activated T lymphocytes. Cell. 1986;46:401. doi: 10.1016/0092-8674(86)90660-4. [DOI] [PubMed] [Google Scholar]
  • 12.Gillis S, Ferm MM, Ou W, Smith KA. T-cell growth factor: parameters of production and quantitative microassay for activity. J Immunol. 1978;120:2027. [PubMed] [Google Scholar]
  • 13.Joshi NN, Mukhopadhyaya R, Advani SH, Gangal SG. Production of Interleukin-2 and expression of Tac antigen in Hodgkin's disease. Cancer Detect Prev [Suppl] 1987;1:137. [PubMed] [Google Scholar]
  • 14.Kronke M, Leonard WJ, Depper JM, Greene WC. Sequential expression of genes involved in human T lymphocyte growth and differentiation. J Exp Med. 1985;161:1593. doi: 10.1084/jem.161.6.1593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Landolfo S, Gariglio M, Gribaudo G, Jemma C, Giovarelli M, Cavallo G. Interferon γ is not an antiviral, but a growth-promoting factor for T lymphocytes. Eur J Immunol. 1988;18:503. doi: 10.1002/eji.1830180403. [DOI] [PubMed] [Google Scholar]
  • 16.Lefkovits I, Waldmann H. In: Limiting dilution analysis of cells in the immune system. Lefkovits I, Waldmann H, editors. London: Cambridge University Press; 1979. pp. 93–114. [Google Scholar]
  • 17.Moghe MV, Advani SH, Gangal SG. Demonstration of inhibitory factors affecting cell mediated immunity in patients with Hodgkin's disease. Eur J Cancer. 1980;16:937. doi: 10.1016/0014-2964(80)90332-1. [DOI] [PubMed] [Google Scholar]
  • 18.Moretta A. Frequency and surface phenotype of human T lymphocytes producing interleukin-2. Analysis by limiting dilution and cell cloning. Eur J Immunol. 1985;15:148. doi: 10.1002/eji.1830150208. [DOI] [PubMed] [Google Scholar]
  • 19.Moretta A, Pantaleo G, Moretta L, Cerottini JC, Mingari MC. Direct demonstration of the clonogenic potential of every human peripheral blood T cell. Clonal analysis of HLA-DR expression and cytolytic activity. J Exp Med. 1983;157:743. doi: 10.1084/jem.157.2.743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Mukhopadhyaya R, Advani SH, Gangal SG. Impairment of T lymphocyte colony formation in Hodgkin's disease: effect of soluble inhibitory factors on normal T lymphocyte colony formation potential. Acta Haematol. 1983;70:357. doi: 10.1159/000206793. [DOI] [PubMed] [Google Scholar]
  • 21.Mukhopadhyaya R, Advani SH, Gangal SG. Effect of exogenous interleukins on in vitro responses of T lymphocytes from patients with Hodgkin's disease. Cancer Detect Prev. 1987;10:445. [PubMed] [Google Scholar]
  • 22.Mullbacher M, Danish CR, Mundy JP. An improved colorimetric assay for T cell cytotoxicity in vitro. J Immunol Methods. 1984;68:205. doi: 10.1016/0022-1759(84)90151-0. [DOI] [PubMed] [Google Scholar]
  • 23.Musatti CC, Yasaka K, Santos LMB. Impaired proliferative response and low Interleukin-2 production in patients with lymphoma. Braz J Med Biol Res. 1987;20:351. [PubMed] [Google Scholar]
  • 24.Petrie A. Lecture notes on medical statistics. Oxford: Blackwell; 1978. pp. 102–128. [Google Scholar]
  • 25.Reed JC, Alpers JD, Nowell PC, Hoover RG. Sequential expression of protooncogenes during lectin stimulated mitogenesis of normal human lymphocytes. Proc Natl Acad Sci USA. 1986;83:3982. doi: 10.1073/pnas.83.11.3982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Ryser JE, Mac-Donald HR. Limiting dilution analysis of alloantigen — reactive T lymphocytes: I Comparison of precursor frequencies for proliferative and cytolytic response. J Immunol. 1979;122:1691. [PubMed] [Google Scholar]
  • 27.Soulillou JP, Douillard JY, Vie H, Harousseau Guenel J, Mevel-Le Pourheit AL, Mevel BL. Defect in lectin-induced IL-2 production by peripheral blood lymphocytes of patients with Hodgkin's disease. Eur J Cancer Clin Oncol. 1985;21:935. doi: 10.1016/0277-5379(85)90111-7. [DOI] [PubMed] [Google Scholar]
  • 28.Stern JB, Smith KA. Interleukin induction of T-cell G1 progression and c-myb expression. Science. 1986;233:203. doi: 10.1126/science.3523754. [DOI] [PubMed] [Google Scholar]
  • 29.Taswell C. Limiting dilution assays for the determination of immunocompetent cell frequencies: 1. Data analysis. J Immunol. 1981;126:1614. [PubMed] [Google Scholar]
  • 30.Vie H, Miller RA. Estimation by limiting dilution analysis of human IL-2 secreting T cells: detection of IL-2 produced by single lymphokine-secreting T cells. J Immunol. 1986;136:3292. [PubMed] [Google Scholar]
  • 31.Webb DR, Goeddel DV. Lymphokines, vol 13. Florida: Academic Press; 1987. [Google Scholar]
  • 32.Zamkoff KW, Reeves WG, Paolozzi FP, Poiesz SJ, Comis RL, Tomar RH. Impaired interleukin regulation of the phytohaemagglutinin response in Hodgkin's disease. Clin Immunol Immunopathol. 1985;35:111. doi: 10.1016/0090-1229(85)90084-4. [DOI] [PubMed] [Google Scholar]

Articles from Cancer Immunology, Immunotherapy : CII are provided here courtesy of Springer

RESOURCES