Impact of systemic histamine deficiency on the crosstalk between mammary adenocarcinoma and T cells.
The purpose of the present study was to investigate the influence of lack of histamine (HA) on tumor growth and functions of T cells in order further to illustrate the mechanism of immunological tolerance induction by HA. We assessed the phenotype and cytokine production of splenic lymphocytes in syngeneic HA-free (histidine decarboxylase knock-out) (HDC KO) and wild-type mice, inoculated subcutaneously with the LM2 murine breast cancer cell line. Relative quantification of target mRNA was performed with a TaqMan real-time RT-PCR assay. The CD4(+)CD25(high+) Treg cell numbers were significantly smaller in the tumor-bearing KO mice than in the wild type ones measured by flow-cytometry. The expression of forkhead box P3 (Foxp3) decreased significantly and the copies of splenic Tbox-21 (T-bet) transcriptional factor mRNA was higher in HDC KO tumor-bearing mice than those of normal mice. The cytokine levels showed that a smaller number of interleukin-13-producing Th2 cells were elicited compared to interferon-gamma-producing Th1 cells in the tumor-bearing HDC KO mice. In conclusion, the present study demonstrates that endogenous histamine stimulates the growth of breast adenocarcinoma tumor implants in mice by suppressing anti-tumor immunity.
Hegyesi
Hargita
H
Department of Genetics, Cell and Immunobiology, SE Nagyvarad ter 4, Budapest, 1089 Hungary. hegyhar@dgci.sote.hu
Colombo
Lucas
L
Pállinger
Eva
E
Tóth
Sára
S
Boer
Katalin
K
Molnár
Viktor
V
Falus
András
A
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006632:Histamine / Q000172:deficiency*; D006640:Histidine Decarboxylase / Q000235:genetics / Q000378:metabolism; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D000098815:T-bet Transcription Factor
D017252:CD3 Complex; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D006632:Histamine; D006640:Histidine Decarboxylase