Cooking Up T Lymphocytes

[Guest guest]

[interesting work continues on understanding how to prompt the growth

of lymphocytes in vitro and in vivo. Suggested here is that T cell

expansion might be helpful in recovering after a transplant. Unsaid

here is the improved understanding of T cells that might lead to

restoration of at least some of the immune function after

conventional chemo in CLL, and in enhancing over-all recovery in CLL

in general.]

Blood, 15 February 2005, Vol. 105, No. 4, pp. 1373-1374.

Cooking up T cells

Warren S. Pear

UNIVERSITY OF PENNSYLVANIA

The Notch ligands Delta-1 and Jagged-1 differentially induce T-cell

development in culture.

Two articles in this issue address how Notch ligands induce T-cell

development. Mammalian Notch ligands comprise 2 families, serrate-

like (Jagged1, Jagged2) and Delta-like (Dll1, 3, and 4). Both

families encode transmembrane proteins whose extracellular domain

contains epidermal growth factor (EGF)–like repeats and an N-terminal

DSL domain (for Delta, Serrate, Lag2) that binds Notch receptors and

short, poorly conserved intracellular domains that have important but

poorly understood functions. Notch receptor binding by ligand

initiates a series of proteolytic cleavages in the receptor, causing

release of the intracellular domain of Notch from the plasma membrane

and translocation into the nucleus, where it creates a short-lived

complex that activates transcription.

<snip>

Although much remains to be learned about the mechanism of Notch-

induced T-cell development, the ability to efficiently generate human

T cells in culture holds great therapeutic promise, such as in

improving T-cell generation after myeloablative therapy. The culture

systems described to date are an excellent start and understanding

the functions of the ligands in producing specific signals will be

important. This hope must be tempered with caution, as it is not yet

known whether the T cells derived from these cultures will have an

increased propensity to cause autoimmune disease or leukemia.

Nevertheless, the advent of these culture systems should allow rapid

progress in addressing these issues and translating these findings to

the clinic.