AGE-ASSOCIATED AND MICROENVIRONMENT-ASSOCIATED INFLUENCES BY PLATELET-DERIVED GROWTH-FACTOR ON T-CELL FUNCTION

Platelet-derived growth factor (PDGF) is produced by numerous cell typ es in response to a variety of activation signals. Although the role o f PDGF in cellular proliferation is well established, the immunomodula tory effects of this peptide growth factor are only now being delineat ed. We previously established that PDGF alters the profile of lymphoki nes produced by activated T cells obtained from the peripheral lymph n odes of adult mice. We now report that T cells residing in lymphoid or gans that receive their major afferent lymphatic drainage from gut muc osa are relatively resistant to the effects of this growth factor. As the vast majority of peripheral T cells are in the recirculating T cel l pool, these findings suggest that tissue-specific microenvironmental factors function to regulate the sensitivity of T cells to PDGF-media ted influences. Additional studies have determined that the norma proc ess of aging is accompanied by a systemic loss in T cell responsivenes s to PDGF. Although the T cells of immature (2-wk-old) and young adult mice are responsive to the immunomodulatory influences of PDGF, T cel ls of aged animals (>100 wk) are relatively resistant to its effects. Some of the immune abnormalities noted to occur during the aging proce ss appear to represent a consequence of the dysregulated production of IL-6. We therefore evaluated whether IL-6 was responsible for modifyi ng the sensitivity of T cells to PDGF. Data presented herein demonstra te that IL-6 abrogates the ability of PDGF to modify lymphokine produc tion by T cells after activation. Therapeutic measures capable of redu cing spontaneous IL-6 production in aged mice restored the ability of their T cells to respond to PDGF, suggesting that the dysregulated pro duction of IL-6 within the aged host interferes with the ability of PD GF to convey important microenvironmental Information to T cells resid ing in peripheral lymphoid organs.