Study Gives Insight into How Immune Cells Divide

05/16/2007

White blood cells known as T cells coordinate immunologic responses focused on a single entity, such as a specific type of bacterial pathogen. As few as one in one million naïve T cells, T cell precursors, are specific for a single type of infection. T cell subtypes are generated when naïve T lymphocytes directly recognize an antigen. Effector T cells initiate the acute response to infection, while memory T cells maintain long-term immunity to infection.

A recent multi-institutional study led by John Chang, M.D., University of Pennsylvania, and colleagues at Children's Hospital, may change the way that researchers think about how our bodies react to infection and how vaccines work, and may ultimately be applied to a more targeted approach to developing vaccines.

Many immunologists thought that when an immune cell receives a signal the "parent" T cell divides into two of the same type of "daughter" cells. However, this study, published in the March issue of Science, found that a "parent" T cell can differentiate into two different types of "daughter" cells following an immune response, one effector T cell and one memory T cell .

Dr. Chang and colleagues looked at how naïve T cells divide after recognizing a bacterial infection. The T cells divided unequally, with certain cellular components and proteins preferentially localized to one of the two poles of division. In T cells that were not stimulated by a specific antigen this unequal division did not occur, suggesting that a specific antigen-directed immunological response is required for the unequal division.

The cells produced by the asymmetric division of T cells exposed to bacterial infection had distinctly different characteristics. In addition, both types of new "daughter" cells consistently arose from the same region of the dividing "parent" cell. The proximal region of the asymmetrically dividing parent cell consistently generated an effector T lymphocyte-like immune cell, while the distal region always became a memory T lymphocyte-like immune cell. These results indicate that asymmetric cell division is significant in determining T lymphocyte cell fate after an immune response.

These results suggest a mechanism by which an immune response in one naïve T cell would ensure that the microbe is eliminated, and long-term immunity remains. This novel paradigm also suggests a new function for immunological synapse, the interface between the naïve T cell and the antigen-presenting cell. The immunological synapse may polarize intracellular and cell surface molecules to different poles of the cell to initiate asymmetric cell division and thus create specialization within dividing T cells.

The Children's Hospital of Philadelphia co-author of this study is Jordan S. Orange, M.D., Ph.D., Division of Allergy and Immunology.