Telocytes (TCs) are a vital constituent of interstitial tissue. They contribute to regulating cell function in heterotypic connections via direct contact or paracrine singling. Few studies mentioned intraepithelial TCs; however, they have been identified with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In this study, we investigated the intraepithelial and interstitial TCs using immunohistochemistry (IHC) and TEM. TCs can be identified by their distinctive telopodes (TPs), which consist of podoms and podomere, using TEM and immunohistochemical staining with CD34, CD117, and VEGF antibodies. Intraepithelial TCs established heterocontact with the lamellar capillary and interstitial TCs connected with the blood vessel in lamina propria. Intraepithelial TCs established direct contact with epithelial cells, which formed the lymph space while interstitial TCs connected with the secondary vascular vessels. The study provides evidence for TCs' heterocontact with lamellar blood capillaries, the blood vessels, chloride cells, and immune cells, such as rodlet cells and lymphocytes. In conclusion, TCs have a role in regulating respiratory activities, maintaining osmotic pressure, modulating the immune response, and conducting immunosurveillance. Research highlights We investigated the intraepithelial and interstitial TCs using immunohistochemistry (IHC) and TEM. TCs can be identified by their distinctive telopodes (TPs), which consist of podoms and podomere, using TEM and immunohistochemical staining with CD34, CD117, and VEGF antibodies. Intraepithelial TCs established heterocontact with the lamellar capillary and interstitial TCs connected with the blood vessel in lamina propria.

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Regulatory T cells (Tregs) are distinct type of T-cells which provide feedback control to any immune response. They are necessary to stop the immune response after the antigen has been successfully recognized. In the tumour micro-environment, the tumour often modulates the immune cells surrounding it in a way that it converts a large population of activated T-cells in to Tregs. For instance, tumours have been known to secrete IL-10 an inhibitory cytokine which is necessary for Treg formation. The tumour also modulates Dendritic cells (DC) and Macrophages so that they secrete inhibitory cytokines and promote tumorigenesis. Commonly, a Treg response to cancer cells, is to suppress the active immune response to the cancer. This review describes the recent studies of Treg cells in different human malignancies and discusses the restoration of antitumor immunity by depletion or reduced the functional strength of Treg cells hence, providing a promising tool to perfectly managing antitumor immune responses.

Introduction:Leukopenia is one of the major side effects of myelosuppressive chemotherapy such as cyclophosphamide (CTX). We and others have used CTX either alone or in combination with G-CSF for the mobilization of hematopoietic stem cells (HSCs). This mobilization can induce expansion of myeloid cells with immunosuppressive phenotype. In this pilot study, we aimed to test whether bone marrow lysate (BML)/CTX, a rich source of growth factors, can lower the expansion of myeloid cells with immunosuppressive phenotypes in tumor-bearing mice without interfering with the anti-tumor effects of CTX or with the mobilization of HSCs.Methods:Female CD1 mice were treated on day 0 with an i.p. injection of Ehrlich ascites carcinoma (EAC). On day 7, the mice were i.p. injected with CTX followed by s.c. injection of G-CSF for 5 consecutive days, single s.c. injection of BML/PBS or BML/CTX or single i.v. injection of BMC/PBS or BMC/CTX.Results:Treatment of EAC-bearing mice with BML/PBS or BML/CTX did not interfere with the anti-tumor effect of CTX. EAC increased the numbers of immature polymorphonuclear cells (iPMN; neutrophils) in both blood and spleen. Treatment of EAC-bearing mice with CTX further increased the numbers of these cells, which were decreased upon treatment with BML/CTX. Treatment with BML/PBS or BML/CTX increased the numbers of stem cells (C.Kit+Sca-1+) in BM; the effect of BML/CTX was higher, but with no significant effect on the numbers of HSCs. Future studies are needed to analyze the molecular components in BM lysate and to determine the underlying mechanisms.

Background: Anti-cancer adoptive T cell therapy has shown significant anti-tumor responses in cancer patients. This therapy is based on in vitro activation of autologous T cells harvested from a cancer patient and infusing them back through blood. The efficacy of adoptively transferred T cells depends on the in vitro conditioning regimen in particular the type of used cytokines. Aim: This study aimed to use toll like receptors (TLRs) ligands (TLRLs) to condition T cells in vitro as a novel approach instead of cytokines. Methods: Spleen cells were harvested from TCR transgenic C57BL/6 pmel-1 mice, in which CD8+ T cells are engineered to recognize melanoma MHC class-I peptides.Unfractionated splenocytes were cultured for 24 hours in vitro with media or melaoma peptide plus or minus IL-12 (10ng/ml), poly(I:C) (TLR3L; 25ug/ml) or CpG (TLR9L; 10ug/ml). Then, activation, proliferation and cytokine production of the cultured cells were assessed. In another set of experiments, the cultured cells were harvested and infused into syngeneic B6 mice followed by vaccination to evaluate their antigen-specific expansion and contraction. Results: Conditioning of donor splenocytes in vitro with the TLR3L or TLR9L during antigen stimulation increased the antigen specific activation, proliferation, and cytokine production. Interestingly, in vitro treatment of the unfractionated splenocytes with TLR9L enhanced the activation and proliferation of B cells regardless antigen stimulation. Adoptive transfer of TLRL-conditioned peptide stimulated CD8+ T cells into naïve mice showed better survival and higher expansion in response to concomitant vaccination with peptide. Interestingly, in vitro conditioning of CD8+ T cells with TLR9L and in vivo conditioning with TLR3L resulted in the best antigen specific expansion of these cells upon their adoptive transfer into recipient mice. Conclusion: These results show that provision of CD8+ T cells in vitro and in vivo with certain TLR agonists can markedly enhance their antigen specific responses upon their adoptive transfer, opening a potential application of this approach in anti-cancer adoptive immunotherapy.