The role of eomesodermin in CD4+ effector T cells differentiation

Dissertant

Arib, Hanani

Thesis advisor

Sindidi, Khalid Sadaqa
Cymerman, Daniel Hirschhorn
Mirghub, Taha

Comitee Members

Berrada, Fuad
al-Asli, Abd al-Ghani
Najmi, Mustafa

University

Al Akhawayn University

Faculty

School of Science and Engineering

University Country

Morocco

Degree

Master

Degree Date

2011

English Abstract

CD4+T cells represent key players of adaptive cellular immune responses.

Antigen-primed naive CD4+T cells differentiate into several subsets of effector T cells with a variety of different functions.

These effector cells secrete a variety of cytokines and coordinate different aspects of adaptive immunity.

Documentations have showed that CD4+T cells are also able to develop cytotoxic function during in vitro culture.

Importantly, Eomesodermin (eomes) plays a key role in directing lytic effector differentiation of CD8+T cells and NK cells.

It is critical for invoking the characteristics of the cytolytic effector lineage including IFN-ɣ, perforin, and granzyme B.

We hypothesized that eomes expression that greatly impact CD8+T differentiation into cytotoxic cells is thought to also affect CD4+T cells in a similar manner.

In order to investigate and tackle the hypothesis from both sides, eomes expression was first ectopically induced in CD4+T cells and then knocked down using shRNA in Trp1 CD4+T cytotoxic cells.

In this regard, ectopic expression of T-box transcription factor eomes in CD4+T cell increased GrzB and IFN-ɣ expression.

However, downregulation of eomes in CD4+ cytotoxic T cells using shRNA was associated with the absence of GrzB expression.

These data suggest a pivotal role of eomes in controlling cytolytic activity and in programming CD4+ cytotoxic T cell differentiation.

Thus, the ability of CD4+T cells to develop cytotoxic function would expand their role in tumor immunity beyond their conventionally assumed role as “helpers” that enhance the function of CD8+T cells and other immune cells.

Moreover, adoptive transfert of CD4+ cytotoxic T cells can be explored in combination with other immunotherapies in the treatment of aggressive tumors including melanoma.

Main Subjects

Biology

Topics

• Immunology

No. of Pages

42

Table of Contents

• APA
• MLA
• AMA

Language

English

Data Type

Arab Theses

Record ID

BIM-629730