γδ T Cell Therapy Development Services for Pathogen Infections

Activation and proliferation of γδ T cells play a significant role in diverse infectious diseases induced by bacteria, viruses, and parasites and exert their potential effector function to effectively eliminate the infection. Creative Biolabs is harnessing the unique properties of γδ T cells to develop potent and targeted pathogen infection disease therapies for research use. We also offer γδ T cell-related protein and antibody products for worldwide customers.

γδ T Cells Recognize Antigens

Infectious diseases are mainly caused by pathogen infections such as viruses, bacteria, and parasites. Dual infection by different types of pathogenic microorganism and secondary infection is a common clinical phenomenon threatening the health of human beings. Nowadays, more and more researchers are focusing on conventional T cells and their subpopulations with different phenotypes instead of the pathogen itself. Though γδ T cells make up a very small proportion of T cells, its various subgroups are widely distributed in different parts of the human body and are attractive effectors for infectious disease immunity. γδ T cells are mainly divided into three subgroups according to the expression of γ and δ chains: Vδ1 T cells, Vδ2 T cells, and Vδ3 T cells.

Vδ1 T cells are mostly found in the mucosal epithelium and are in connection with the infection of many pathogens, such as cytomegalovirus (CMV), Listeria monocytogenes (L. monocytogenes) and human immunodeficiency virus (HIV). Vδ2 T cells also exhibit their effective immune response to bacteria and viruses such as mycobacteria, influenza viruses, and Epstein-Barr virus (EBV) like Vδ1 T cells. Vδ3 T cells, the smallest subset of γδ T cells, are abundant in the liver and are mainly involved in the process of chronic viral infections. Different from αβ T cells, γδ T cells can recognize various types of antigens without restrictive major histocompatibility complex (MHC) molecules and exert their protective function in elimination of pathogens and tissue repair via producing chemokines, cytokines, lytic enzymes, cytotoxic and noncytolytic antiviral activities.

Fig.1 γδ T cell recognizes antigens. (Zhao, 2018)

γδ T Cell Therapy in Various Infectious Diseases

• γδ T cells play a significant role in Mycobacterium tuberculosis (MTB) infection. Among various subgroups, Vγ9Vδ2 T cells which exist in humans and the vast majority of nonhuman primates carry huge weight in mycobacterial infections. It recognizes HMBPP ((E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate) via forming tight complexes following binding with BTN3A1 during MTB infection. MTB phosphoantigen-activated γδ T cell produces TNF-α and IFN-γ to enhance the protective responses to MTB. Meanwhile, cytolytic effector function based on granulysin and perforin is essential for γδ T cells to defend against MTB infections.
• IL-17A is mainly produced by γδ T cells during L. monocytogenes infection to promote innate and adaptive immune responses, and it promotes host function of effective elimination of infection by producing cytokines and CXC chemokines.
• Phosphoantigen-activated γδ T cells secret substances associated with killing cells infected by influenza viruses to fight against viruses, such as perforin, granzyme B, and granulysin.
• Different from other viral infections, HIV does not depend on any γδ T cell subset alone but need two primary subsets of γδ T cells to participate together. Vδ1 and Vδ2 T cells in good proportion would play a key role in HIV infections.
• Natural killer (NK) cells and Vγ9Vδ2 T cells exert their cytotoxic lymphocyte function against EBV infection.
• Vδ1 T cells are expanded in liver diseases such as viral hepatitis and defense against liver damage by producing increased cytotoxicity and inflammatory cytokine.
• Accumulating findings indicate that γδ T cells play a key role in defending against Plasmodium infection. Vγ9Vδ2T cells activated by P. falciparum antigens produce cytotoxic granules to kill merozoites and control parasite density during the blood stage of infection.

Parasitic Infections Plasmodium Infections and Human Malaria Influenza Infections Mycobacteria Infections Listeria monocytogenes Infections Cytomegalovirus Infections HIV Infections Epstein-Barr Virus Infections Hepatitis B Virus Infections Hepatitis C Virus Infections

γδ T Cell Therapy for Pathogen Infections

γδ T Cell-Based Services

γδ T cell-based preclinical or clinical research emphasizes the importance of host immune response instead of pathogens themselves. Since the diverse subpopulations of γδ T cells possess different biological characteristics, all of them could be utilized to play different roles in various infectious illnesses. Besides, γδ T cells could be combined with chimeric antigen receptor (CAR) T-cell, immune checkpoint inhibitors, hematopoietic stem cell transplantation (HSCT) to exert their potential effector function to effectively eliminate the infection. γδ T cells also could be used for vaccine development.

There are many different γδ T cell surface markers such as CCR5, CCR6, CD83, CD161, CXCR4 and factors secreted by γδ T cells such as IL 2/4/5/6/10/12/13/22, transforming growth factor beta 1 (TGF-beta), TNF-alpha (tumor necrosis factor alpha). Transcription factors involved in γδ T cell development include EOMES, GATA-3, promyelocytic leukemia zinc finger (PLZF), ROR gamma t/RORC2/NR1F3, T-box transcription factor TBX21. Creative Biolabs provides γδ T Cell Proteins and γδ T Cell Antibody products against these targets.

Creative Biolabs has developed and optimized in-house proprietary platforms for selective isolation and expansion of specific γδ T cell populations from human tissues. Our technologies aim to facilitate the development and access to cost-effective allogeneic cell therapies in the academic area. If you are interested in γδ T cell development services for pathogen infections, please feel free to contact us.

Reference

1. Zhao, Y.; et al. Protective role of γδ T cells in different pathogen infections and its potential clinical application. Journal of immunology research. 2018, 2018.