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*
National Institute of Immunology, New Delhi, India;
Rosenstiel Basic Medical Sciences Research Center and Department of Biology, Brandeis University, Waltham, MA 02254; and
Department of Biological Sciences, University of Arkansas, Fayetteville, AR 72701
Naive T cells appear to be primed by specific Ag to differentiate
into either effectors or memory cells. We have been analyzing the
factors involved in this differential commitment in the priming of
alloresponsive human T cells in vitro and have shown that the presence
of a phosphodiesterase inhibitor, pentoxifylline (POX), during priming
results in a decrease in the primary response and enhancement in the
secondary proliferative response. We now show that the POX-mediated
effect can be mimicked by dibutyryl cAMP. The secondary response
enhancement is due to the effects of POX on the T cells rather than the
APCs, because even fixed APCs can prime T cells in the presence of POX.
POX affects T cells directly by increasing clonal frequency rather than
the burst size of the secondary responders. The known inhibition of
IL-2 production by POX is not responsible for this effect, because
exogenous IL-2 supplementation does not block it. The presence of POX
during priming alters the outcome of T cell activation, resulting in a
lower frequency of cells expressing IL-2R
(CD25) and a decrease in
their subsequent apoptosis, and this anti-apoptotic effect is
consistent with the enhanced commitment of T cells to secondary
responsiveness by POX.
This article has been cited by other articles:
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  M. Vig, A. George, R. Sen, J. Durdik, S. Rath, and V. Bal Commitment of Activated T Cells to Secondary Responsiveness Is Enhanced by Signals Mediated by cAMP-Dependent Protein Kinase A-I Mol. Pharmacol., December 1, 2002; 62(6): 1471 - 1481. [Abstract] [Full Text] [PDF]
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 R. Suresh, M. Vig, S. Bhatia, E. P. B. Goodspeed, B. John, U. Kandpal, S. Srivastava, A. George, R. Sen, V. Bal, et al. Pentoxifylline Functions As an Adjuvant In Vivo to Enhance T Cell Immune Responses by Inhibiting Activation-Induced Death J. Immunol., October 15, 2002; 169(8): 4262 - 4272. [Abstract] [Full Text] [PDF]
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Y. Sun, L. Li, F. Lau, J. A. Beavo, and E. A. Clark Infection of CD4+ Memory T Cells by HIV-1 Requires Expression of Phosphodiesterase 4 J. Immunol., August 15, 2000; 165(4): 1755 - 1761. [Abstract] [Full Text] [PDF]
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