NATURAL KILLER T CELLS IN HEPATIC LEUCOCYTE INFILTRATES IN PATIENTS WITH MALIGNANT PROCESS AND VIRAL HEPATITIS
https://doi.org/10.15789/1563-0625-2010-1-2-20-40
Abstract
Morphology, topography, and immunohistochemical features of leukocyte infiltrates were studied in various sites of the liver samples from the patients with metastatic disease, been affected by hepatitis B and C viruses at different degree of activity. Liver of СВА mice with implanted САО-1 tumour was also under study. Histochemical, and functional features, as well as immune phenotype of these cells were investigated. It has been shown that the major fraction of leukocyte infiltrates, mostly associated with implanted tumours in experimental mice, and in the areas adjacent to the tumor in humans, like as on the peak of viral hepatitis activity, is composed of lymphocytes. They are presented by large numvers of activated proliferating and differentiating cells bearing specific antigens, as well as natural killers and T-lymphocytes, possessing high-level killer activity towards NK-sensitive, and autologous lines of cancer cells. Hence, the results of our study, generally, confirm the data from literature reporting on existence of a special lymphocyte subpopulation, NKT cells, in human or murine liver affected by hepatitis virus or malignant tumors. The data concerning functional properties of these cells may be used for development of immunotherapy methods of viral diseases and oncological conditions complicated by liver metastases.
About the Authors
O. V. Lebedinskaya
ГОУ ВПО «Пермская государственная медицинская академия им. академика Е.А. Вагнера МЗ РФ», г. Пермь
Russian Federation
Russian Federation
I. N. Kabanovskaja
ГОУ ВПО «Пермская государственная медицинская академия им. академика Е.А. Вагнера МЗ РФ», г. Пермь
Russian Federation
Russian Federation
N. K. Akhmatova
ГУ «Научно-исследовательский институт вакцин и сывороток им. И.И. Мечникова РАМН», Москва
Russian Federation
Russian Federation
E. A. Lebedinskaya
ГОУ ВПО «Пермская государственная медицинская академия им. академика Е.А. Вагнера МЗ РФ», г. Пермь
Russian Federation
Russian Federation
A. V. Lazareva
ГОУ ВПО «Московская государственная медицинская академия им. И.М. Сеченова», Москва
Russian Federation
Russian Federation
M. V. Kiselevsky
ГУ «Российский онкологический научный центр им. Н.Н. Блохина», Москва
Russian Federation
Russian Federation
References
1. Chang Y.J., Huang J.R., Tsai Y.C., Hung J.T., Wu D., Fujio M., Wong C.H., Yu A.L. Potent immune-modulating and anticancer effects of NKT cell stimulatory glycolipids // Proc. Natl. Acad. Sci. USA. – 2007. – Vol. 104, N 25. – P. 10299-10304.
2. Crowe N.Y., Uldrich A.P., Kyparissoudis K., Hammond K.J., Hayakawa Y., Sidobre S., Keating R., Kronenberg M., Smyth M.J., Godfrey D.I. Glycolipid antigen drives rapid expansion and sustained cytokine production by NKT cells // J. Immunol. – 2003. – Vol. 171. – P. 4020-4027.
3. Dhodapkar M.V., Geller M.D., Chang D.H., Shimizu K., Fujii S., Dhodapkar K.M., Krasovsky J. A reversible defect in natural killer T cell function characterizes the progression of premalignant to malignant multiple myeloma // J. Exp. Med. – 2003. – Vol. 197. – P.1667-1676.
4. Exley M.A., Koziel M.J. To Be or Not to Be NKT: Natural Killer T Cells in the Liver // Hepatology. – 2004. – Vol. 40, N 5. – P. 1033-1040.
5. Exley M.A., He Q., Cheng O., Wang R.J., Cheney C.P., Balk S.P., Koziel M.J. Cutting edge: compartmentalization of Th1-like noninvariant CD1dreactive T cells in hepatitis C virus-infected liver // J. Immunol. – 2002. – Vol. 168. – P. 1519-1523.
6. Fuji N., Ueda Y., Fujiwara H., Toh T., Yoshimura T., Yamagishi H. Antitumor effect of a-galactosylceramide (KRN7000) on spontaneous hepatic metastases requires endogenous interleukin 12 in the liver // Clinical Cancer Research. – 2000. – Vol. 6, N 8. – P. 3380-3387.
7. Fuji S., Shimizu K., Smith C. Activation of natural killer T cells by alpha-galactosylceramide rapidly induces the full maturation of dendritic cells in vivo and thereby acts as an adjuvant for combined CD4 and CD8 T cell immunity to a coadministered protein // J. Exp. Med. – 2003. – Vol. 198. – P. 267-279.
8. Godfrey D.I., MacDonald H.R., Kronenberg M.M., Smyth M.J., Van Kaer L. NKT cells: what’s in a name? // Nat. Rev. Immunol. – 2004. – Vol. 4. – P. 231-237.
9. Hammond K.J.L., Pelikan S.B., Crowe N.Y., Randle-Barrett E., Nakayama T., Taniguchi M., Smyth M.J., van Driel I.R., Scollay R., Baxter A.G., Godfrey D.I. NKT cells are phenotypically and functionally diverse // Eur. J. Immunol. – 1999. – Vol. 29. – P. 3768-3781.
10. Kakimi K., Guidotti L.G., Koezuka Y., Chisari F.V. Natural killer T cell activation inhibits hepatitis B virus replication in vivo // J. Exp. Med. – 2000. – Vol. 192, N 7. – P. 921-930.
11. Kenna T., Mason L.G., Porcelli S.A., Koezuka Y., Hegarty J.E., O’Farrelly C., Doherty D.G. NKT cells from normal and tumor-bearing human liver are phenotypically and functionally distinct from murine NKT cells // J. Immunol. – 2003. – Vol. 166, N 11. – P. 6578-6584.
12. Kenna T., Mason L.G., Porcelli S.A., Koezuka Y., Hegarty J.E., O’Farrelly C., Doherty D.G. NKT cells from normal and tumor-bearing human livers are phenotypically and functionally distinct from murine NKT cells // J. Immunol. – 2003. – Vol. 171. – P. 1775-1779.
13. Kenna T., Golden-Mason L., Porcelli S.A., Koezuka Y., Hegarty J.E., O’Farrelly C., Doherty D.G. CD1 expression and CD1-restricted T cell activity in normal and tumour-bearing human liver // Cancer Immunol Immunother. – 2007. – Vol. 56, N 4. – P. 563-72.
14. Kikuchi A., Nieda M., Koezuka Y., Ishihara S., IshikawaY., Tadokoro K., Durrant S., Boyd S., Juji T., Nicol A. In vitro anti-tumour activity of alphagalactosylceramide-stimulated human invariant Valpha24 + NKT cells against melanoma // Br. J. Cancer. – 2001. – Vol. 85. – P. 741-746.
15. Kitamura H., Iwakabe K., Yahata T., Nishimura S., Ohta A., Ohmi Y., Sato M., Takeda K., Okumura K., Van Kaer L., Kawano T., Taniguchi M., Nishimura T. The natural killer T (NKT) cell ligand alpha-galactosylceramide demonstrates its immunopotentiating effect by inducing interleukin (IL)-12 production by dendritic cells and IL-12 receptor expression on NKT cells // J. Exp. Med. –1999. – Vol. 189. – P. 1121-1127.
16. Kronenberg M. Toward an understanding of NKT cell biology: progress and paradoxes // Annual review of immunology. – 2005. – Vol. 23. – P. 877-900.
17. Levy O., Orange J.S., Hibberd P., Steinberg S., LaRussa P., Weinberg A., Wilson S.B., Shaulov A., Fleisher G., Geha R.S., Bonilla F.A., Exley M. Disseminated varicella infection due to the vaccine strain of varicella-zoster virus, in a patient with a ovel deficiency in natural killer T cells // J. Infect. Dis. – 2003. – Vol. 188. – P. 948-953.
18. Matsuda J.L., Gapin L., Baron J.L., Sidobre S., Stetson D.B., Mohrs M., Locksley R.M., Kronenberg M. Mouse V alpha 14i natural killer T cells are resistant to cytokine polarization in vivo // Proc. Natl. Acad. Sci. U. S. A. – 2003. – Vol. 100. – P. 8395-8400.
19. Metelitsa L.S., Naidenko O.V., Kant A., Wu H.W., Loza M.J., Perussia B., Kronenberg M., Seeger R.C. Human NKT cells mediate antitumor cytotoxicity directly by recognizing target cell CD1d with bound ligand or indirectly by producing IL-2 to activate NK cells // J. Immunol. – 2001. – Vol. 167. – P. 3114-3122.
20. Motohashi S., Kobayashi S., Ito T., Magara K.K., Mikuni O., Kamada N., Iizasa T., Nakayama T., Fujisawa T., Taniguchi M. Preserved IFN-alpha production of circulating V alpha 24 NKT cells in primary lung cancer patients // Int. J. Cancer. – 2002. – Vol. 102. – P. 159-165.
21. Pillai A.B., George T.I., Dutt S., Teo P., Strober S. NKT cells can prevent graft-versushost disease and permit graft antitumor activity after bone marrow transplantation. // J. Immunol. – 2007. – Vol. 178, N 10. – P. 6242-51.
22. Poulton L.D., Smyth M.J., Hawke C.G., Silveira P., Shepherd D., Naidenko O.V., Godfrey D.I., Baxter A.G. Cytometric and functional analyses of NK and NKT cell deficiencies in NOD mice // Int. Immunol. – 2001. – Vol. 13. – P. 887-896.
23. Seino K., Motohashi S., Fujisawa T., Nakayama T., Taniguchi M. Natural killer T cellmediated antitumor i mmune responses and their clinical applications // Cancer Sci. – 2006. – Vol. 97, N 9. – P. 807-812.
24. Smyth M.J., Godfrey D.I. NKT cells and tumor immunity-a double-edged sword // Nat. Immunol. – 2000. – Vol. 1. – P. 459-460.
25. Smyth M.J., Crowe N.Y., Takeda K. NKT cells – conductors of tumor immunity? // Curr. Opin. Immunol. – 2002. – Vol. 14. – P. 165-171.
26. Sonoda K.H., Taniguchi M., Stein-Streilein J. Long-term survival of corneal allografts is dependent on intact CD1d-reactive NKT cells // J. Immunol. – 2002. – Vol. 168. – P. 2028-2034.
27. Spadaro M., Curcio C., Varadhachary A., Cavallo F., Engelmayer J., Blezinger P., Pericle F., Forni G. Requirement for IFN-gamma, CD8+ T lymphocytes, and NKT cells in talactoferrininduced inhibition of neu + tumors // Cancer Res. – 2007. – Vol. 67, N 13. – P. 6425-32.
28. Swann J.B., Coquet J.M., Smyth M.J., Godfrey D.I. CD1-restricted T cells and tumor immunity // Curr. Top. Microbiol. Immunol. –2007. – Vol. 314. – P. 293-323.
29. Trobonjaca Z., Leith user F., M ller P., Schirmbeck R., Reimann J. Activating immunity in the liver. I. Liver dendritic cells (but not hepatocytes) are potent activators of IFNγ release by liver NKT cells // J. Immunol. – 2001. – Vol. 167, N 3. – P. 1413-1422.
30. Trobonjaca Z., Kroger A., Stober D., Leith user F., M ller P., Hauser H., Schirmbeck R., Reimann J. Activating immunity in the liver. II. IFNb attenuates NK cell-dependent liver injury triggered by liver NKT cell activation // J. Immunol. – 2002. – Vol. 168, N 8. – P. 3763-3770.
31. Wilson S.B., Delovitch T.L. Janus-like role of regulatory iNKT cells in autoimmune disease and tumour immunity // Nat. Rev. Immunol. – 2003. – Vol. 3. – P. 211-222.
Review
For citations:
Lebedinskaya O.V., Kabanovskaja I.N., Akhmatova N.K., Lebedinskaya E.A., Lazareva A.V., Kiselevsky M.V. NATURAL KILLER T CELLS IN HEPATIC LEUCOCYTE INFILTRATES IN PATIENTS WITH MALIGNANT PROCESS AND VIRAL HEPATITIS. Medical Immunology (Russia). 2010;12(1-2):20-40. (In Russ.) https://doi.org/10.15789/1563-0625-2010-1-2-20-40
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