SUPPRESSED EXPRESSION OF CD80 (B7.1) AND CD86 (B7.2) RECEPTORS IN TAMS UP REGULATED BY AUTOLOGOUS HSP70 PEPTIDE COMPLEX IN DALTONS LYMPHOMA BEARING BALB/C MICE
Pramod Kumar Gautam
Department of zoology, Faculty of Science, Banaras Hindu University, Varanasi-221005, U.P., India
A. Acharya
Department of zoology, Faculty of Science, Banaras Hindu University, Varanasi-221005, U.P., India
Receiving Date:
2015-05-31
Acceptance Date:
2015-06-28
Publication Date:
2015-07-29
Download PDF
Abstract
Co-stimulatory molecules (CSMs) are member of immunoglobulin (Ig) superfamily receptors which
expressed on macrophages. CSMs play important role in the stimulation of cell mediated immune
responses and play important role in the activation of T cells. Activation of T cells is thought to require
two different signals. The first signal (recognition) requires interaction of the T cell receptor with an
antigen bound Major histocompatibility complex (MHC) and the second signal is provided by the CD80
or CD86 on the antigen presenting cell and CD28 and CTLA-4 on the reacting T cell. In the aberration of
proper co-stimulatory signal, the T cell undergoes anergy state instead of activation which favors the
tumor progression. During tumor progression, tumor microenvironment downregulate the expression of
CSMs in M1 phenotype and function and transform into M2 phenotype facilitate tumor progression.
Heat shock proteins 70 (Hsp70) are highly conserved group of cytosolic protein which have important
role in growth, homeostasis. Hsp70 is activator of macrophages and enhances the release of specific and
nonspecific effector molecules that have major role in tumor destruction and immunopotentiation of host.
It has been observed that Hsp70 preparations derived from normal tissues do not elicit tumor immunity,
while Hsp70 preparation derived from tumor cell able to elicit tumor immunity. However, this study
examined the expression of CD80 and CD86 along with Hsp70-peptide complex over the tumor
infiltrating TAMs to assess their significance in Leukemia. Study shows that a remarkable decline in
CSMs expression in M2 phenotypes, which was recovered after Hsp70-peptide complex treatment. These
findings suggest that CSMs might be involved in tumor progression when their expression down regulated
while Hsp70-peptide treatment enhances the expression in TAMs that facilitate tumor regression by
activating T cell.
Keywords:
Co-stimulatory molecules: TAMs: Tumor; Macrophages: Hsp70 peptide complex
References
- Forngaleg-Behia EB, Doseff AI. Regulation of monocytes and macrophages cell fate. Front Bios 2008;14:2413-31.
- Lewis CE, Pollard JW. Distinct Role of Macrophages in Different Tumor Microenvironments. Can Res 2006;66(2):605-12.
- Subauste CS, Malefyt RDW, Fuh F. Role of CD80 (B7.1) and CD86 (B7.2) in the Immune Response to an Intracellular Pathogen. J Immunol 1998;160:1831-40.
- Costello RGT, Mallet FO, Sainty D, et al. Regulation of CD80/B7-1 and CD86/B7-2 molecule expression in human primary acute myeloid leukemia and their role in allogenic immune recognition. Eur J Immunol 1998;28:90–03
- Azuma M, Ito D, Yagita H, Okumura K, Phillips JH, Lanier LL, Somoza C. B70 antigen is a second ligand for CTLA-4 and CD28. Nature 1993;366:76-79.
- Freeman GJ, Gribben JG, Boussiotis VA, Ng JW, Restivo VA Jr, Lombard LA, Gray GS, Nadler LM. Cloning of B7-2: a CTLA-4 counter- receptor that costimulates human T cell proliferation. Science 1993;262:909-11.
- Freeman GJ, Freedman AS, Segil JM, Lee G, Whitman JF, Nadler LM. B7, a new member of the Ig superfamily with unique expression on activated and neoplastic B cells. J Immunol 1989;143(8):2714-22.
- Olive D, Pages F, Klasen S, Battifora M, Costello R, Nunes J, Truneh A, Ragueneau M et. al. Stimulation via the CD28 molecule: Regulation of signaling, cytokine production and cytokine receptor expression. Fundam Clin Immunol 1994;2:185–97.
- June CH, Bluestone JA, Nadler LM, and Thompson CB. The B7 and CD28 receptor families. Immunol Today 1994;15:321–31.
- Schultze J, Nadler LM, and Gribben JG. B7- mediated costimulation and the immune response. Blood Rev 1996;10:111–27.
- Guinan EC, Gribben JG, Boussiotis VA, Freeman GJ, and Nadler LM. Pivotal role of the B7:CD28 pathway in transplantation tolerance and tumor immunity. Blood 1994;84: 3261– 82.
- Lenschow DJ, Walunas TL, Bluestone JA. CD28/B7 system of T cell costimulation. Annu Rev Immunol 1996;14:233-58.
- Harding FA, McArthur JG, Gross JA, Raulet DH, Allison JP. CD28- mediated signalling costimulates murine T cells and prevents induction of anergy in T-cell clones. Nature 1992; 356:607-09.
- Tamura H, Dan K, Tamada K, Nakamura K, Shioi Y, Hyodo Hideya. Expression of Functional B7-H2 and B7.2 Costimulatory Molecules and Their Prognostic Implications in De novo Acute Myeloid Leukemia. Clin Can Res 2005;11:5708-17
- Mantovani A, Sozzani S, Locati M, Allavena P and Sica A. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trend Immunol 2002;11:549-55.
- Bingle L, Brown NJ, Lewis CE. The role of tumor-associated macrophages in tumor progression: implications for new anticancer therapies. J Pathol 2002;3:254-65.
- Sarireh BL and. Eremin O. Tumor-associated macrophages (TAMS): disordered function, immune suppression and progressive tumor growth. J R Coll Surg 2000;45:1-16
- Mahoney KH, Heppner GH. Facs analysis of tumor- associated macrophages replication: differentiation between metastasis and nonmetastasic murine mammary tumor. J leuko Boil 1987;41:205-11.
- Solinas G, Germano G, Mantovani A, and Allavena AP, et al. Tumor-associated macrophages (TAM) as major players of the cancer-related Inflammation. J leuko boil 2009; 86:1065-73.
- Siveen KS and Kuttan G. Role of macrophage in tumor progression. Immunol lett 2009; 123:97-02.
- Jattela M. Heat shock proteins as cellular lifeguards. Ann Med 1999;31:261-71.
- Tamura Y, Peng P, Liu K et al. Immunotherapy of tumors with autologous tumor-derived heat shock protein preparations. Science 1997;278:117-20.
- Udono H, Srivastava PK. Heat shock protein 70-associated peptides elicit specific cancer immunity. J Exp Med 1993;178:1391-96.
- Tokuda Y, Tsuji M, Yamazaki M et al. Augmentation of murine tumor necrosis factor production by amphotericin B in vitro and in vivo. Antimicrob Agents Chemother 1993; 37:2228-30.
- Blachere NE, Li Z, Chandawarkar RY, Suto R, Jaikaria S, Basu S, et al. Heat shock proteinpeptide complexes, reconstituted in vitro, elicit peptide-specific cytoxic T-lymphocytes response and tumor immunity. J Exp Med 1997;186:1315-27.
- Peng P, Menoret A and Srivastava PK. Purification of immunogenic heat shock protein 70- peptide complexes by ADP-affinity chromatography. J Immunol Meth 1997; 204:13-21.
- Shahoo NC, Rao KVS, Natrajan K. CD80 expression is induced on activated B cell following Stimulation by CD86. Scnd J immunol 2002;55:577:84.
- Lahat N, Rahat MA, Ballan M, Weiss-Cerem L, Engelmayer M, Bitterman H. Hypoxia reduces CD80 expression on monocytes but enhances their LPS-stimulated TNF-α secretion. J Leukoc Biol 2003;4(2):197-5.
- Friedemann K, Wolfgang FV, Ruediger A. Signal transduction and co-stimulatory pathways. Transp Immunol 2002;9:69–82.
- Kuchroo VK, Das MP, Brown JA, Ranger AM., Zamvil SS, Sobel RA, Weiner HL, Nabavi N, Glimcher LH. B7–1 and B7–2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: application to autoimmune disease therapy. Cell 1995; 80:707–18.
- Harris NL, Prout M, Peach RJ, Fazekas DSG, B Ronchese, F. CD80 costimulation is required for Th2 cell cytokine production but not for antigen-specific accumulation and migration into the lung. J. Immunol 2001;166:4908–14.
- Anderson DE, Sharpe AH, Hafler DA. The B7-CD28/ CTLA-4 costimulatory pathways in autoimmune disease of the central nervous system. Curr Opin Immunol 1999;11:677–83.
- Kumar S, Deepak P, Acharya A. Hsp70 induces Th1 polarization through tumor-associated macrophages in a T-cell lymphoma. Neoplasma 2007;54(2):113–22.
- Gautam PK, Kumar S, Deepak P, Acharya A. Morphological effects of autologous hsp70 on peritoneal macrophages in a murine T cell lymphoma. Tumor Biol 2013;34:3407–15.
- Simone M, Clara B, Pierluigi P. Coinhibitory molecules in cancer biology and therapy. Cyto& Grow Fact Revi 2013;24:147–61.
- Lin RY, Saha DC, Bernstein CJ, Astiz ME, Rackow EC. The pattern of inflammation in rat sepsis due to enterotoxin-producing staphylococcus aureus: a comparison with ischemiareperfusion injury. J Med 1996; 25:303–17.
- Takada M, Chandrakerm A, Nadeaum KC, Sayeghm MH, Tilneym NL. The role of the B7 co-stimulatory pathway in experimental cold ischemia/reperfusion injury. J Clin Invest 1997;100:1199–03.
Back
