NAIVE MURINE NEONATAL T-CELLS UNDERGO APOPTOSIS IN RESPONSE TO PRIMARY STIMULATION

The cellular mechanisms controlling deficient immune responses in newb orn animals are not well understood. Our earlier studies showed that d evelopmental regulation of Th cell activity may be one of the major ca uses of immunodeficiency in neonatal animals. Naive murine neonatal T cells showed poor Th1 activity but robust Th2 activity in response to primary stimulation in vitro. Although they produced high levels of IL -4, neonatal T cells proliferated poorly, suggesting that neonatal T c ell survival in primary cultures may be limited. We show here that, un like adult T cells, naive neonatal T cells undergo apoptosis in respon se to primary TCR-mediated stimulation. Ligation of the TCR alone, in the absence of accessory cell costimulation, is sufficient to induce a poptosis. Moreover, CD4(+) and CD8(+) T cells show equivalent levels o f apoptosis, Lastly, this apoptosis can be prevented by the addition o f excess IL-2 or by conditions promoting a high level of IL-2 producti on (TCR-independent stimulation, anti-CD28 mAb, or exogenous IL-6) by neonatal T cells. However, IL-2 alone is not sufficient to support fun ctional rescue from apoptosis; only IL-6 supports the ability of these cells both to survive and to mount vigorous secondary responses. The identification of conditions allowing functional rescue from apoptosis in vitro has important implications for enhancing vaccine responsiven ess in vivo.