Modulation of CD8+ T-cell differentiation state following stimulation with interleukin-7 (IL-7) (meeting abstract).

Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.

Modulation of CD8+ T-cell differentiation state following stimulation with interleukin-7 (IL-7) (meeting abstract).

FASEB J; 6(5):A1698 1992. Unique Identifier : AIDSLINE ICDB/93687598
Feeney LA; Fredericks KH; Harvey SE; Okarma TB; Moody DJ; Applied Immune Sciences, Inc., Menlo Park, CA

Abstract: Extracorporeal manipulation of autologous T cells is used in clinical trials for the treatment of cancer and AIDS. Most of these approaches depend upon the ex vivo production of large numbers (greater than 10(10)) of effector cells. Two key improvements that can be made to improve the efficiency of this process would be to increase the effector frequency and to elevate the state of activation of these same cells. Covalently bound monoclonal anti-CD8 antibody has been used to successfully concentrate the CD8+ effector pool from both peripheral blood and solid tumors in a therapeutically acceptable format. We have hypothesized that fewer effector cells will need to be administered if the population effector potency is amplified. Peripheral blood isolated CD8+ T cells, activated with interleukin-2 (IL-2), exhibited a rapid induction of IL-7 receptor expression between day 0 and day 2 ex vivo, followed by a slower rate of induction through day 9 ex vivo. Treatment of day 7 ex vivo CD8+ cells with recombinant IL-7 (1000 U/ml) for up to 48 hr produced increases in cytolytic serine esterase levels of up to 52%. Surface membrane expression of the adhesion molecule associated with cell-to-cell contact (ICAM-2, ie, CD54) was elevated in 9/14 rIL-7-pulsed cultures. Polymerase chain reaction analysis of the mRNA from the treated CD8+ cultures detected the presence of mRNA for perforin, serine esterase, interferon (gamma), as well as tumor necrosis factor (beta). Treatment of the CD8+ cells with rIL-7 did not appreciably modulate the size of cDNA bands associated with these proteins. The data lead us to conclude that rIL-7 can enhance the potential binding characteristics and lytic mechanisms of rIL-2 propagated CD8+ effector cells, with little impact on the production of effector molecules.

Keywords: Cell Adhesion Molecules/METABOLISM Cell Communication Cell Differentiation/*DRUG EFFECTS DNA/METABOLISM Interferon Type II/METABOLISM Interleukin-7/*PHARMACOLOGY Membrane Proteins/GENETICS Neoplasms/PATHOLOGY RNA, Messenger/METABOLISM T-Lymphocytes, Suppressor-Effector/*CYTOLOGY Tumor Necrosis Factor/METABOLISM ABSTRACT
930228
M9320865

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