The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/10/1013/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 7, October 4, 1999 1013-1024

Interleukin 2, but Not Other Common {gamma} Chain–binding Cytokines, Can Reverse the Defect in Generation of CD4 Effector T Cells from Naive T Cells of Aged Mice

Laura Haynesa, Phyllis-Jean Lintonb, Sheri M. Eatona, Susan L. Tonkonogyc, and Susan L. Swaina
a Trudeau Institute, Saranac Lake, New York 12983
b Sidney Kimmel Cancer Center, San Diego, California 92121
c North Carolina State University, Raleigh, North Carolina 27606

Correspondence to: Laura Haynes, Trudeau Institute, P.O. Box 59, Saranac Lake, NY 12983. Tel:518-891-3080 ext. 143 Fax:518-891-5126 E-mail:lhaynes{at}trudeauinstitute.org.

Development of effectors from naive CD4 cells occurs in two stages. The early stage involves activation and limited proliferation in response to T cell receptor (TCR) stimulation by antigen and costimulatory antigen presenting cells, whereas the later stage involves proliferation and differentiation in response to growth factors. Using a TCR-transgenic (Tg+) model, we have examined the effect of aging on effector generation and studied the ability of {gamma}c signaling cytokines to reverse this effect. Our results indicate that responding naive CD4 cells from aged mice, compared with cells from young mice, make less interleukin (IL)-2, expand poorly between days 3 to 5, and give rise to fewer effectors with a less activated phenotype and reduced ability to produce cytokines. When exogenous IL-2 or other {gamma}c signaling cytokines are added during effector generation, the Tg+ cells from both young and aged mice proliferate vigorously. However, IL-4, IL-7, and IL-15 all fail to restore efficient effector production. Only effectors from aged mice generated in the presence of IL-2 are able to produce IL-2 in amounts equivalent to those produced by effectors generated from young mice, suggesting that the effect of aging on IL-2 production is reversible only in the presence of exogenous IL-2.

Key Words: T cell receptor transgenic, CD4 cells, aging, IL-2, {gamma}c-binding cytokines


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