Impact of Systemic Histamine Deficiency on the Crosstalk Between Mammary Adenocarcinoma and T Cells

Abstract

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-γ-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.