CD28 COSTIMULATION INHIBITS TCR-INDUCED APOPTOSIS DURING A PRIMARY T-CELL RESPONSE

Murine splenic T cells undergo apoptosis when the TCR complex is re-cr oss-linked in the absence of costimulation during a primary immune res ponse, However, if the CD28 complex is also cross-linked, growth conti nues without induction of apoptosis, Prevention of apoptosis by CD28 c ostimulation was associated with increased expression of bcl-x(L), whi le overexpression of bcl-2 in T cells from bcl-2 transgenic mice was n ot protective, In both situations, surviving cells can be recovered in a growth-arrested state following the primary response, many more if CD28 was also religated, When these cells were restimulated in a secon dary response, those surviving TCR religation without CD28 costimulati on could not be induced to proliferate further, In contrast, cells giv en CD28 costimulation during the primary response proliferated well af ter restimulation, Thus the CD28 signaling pathway may function not on ly in the initial activation of naive T cells, but also in maintaining their viability and responsiveness during a primary immune response, In addition, the results further suggest that bcl-2 and bcl-x(L) regul ate T cell survival under different conditions, with bcl-x(L) being pe rhaps more important in maintaining viability of activated T cells tra versing the cell cycle.