|
pubmed:abstractText |
Clonotype-positive (1B2+) T cells from 2C T cell receptor (TCR) transgenic mice were used to define the role of CD8 molecules in the induction phase vs. the effector phase of the primary response to class I alloantigens. Three main findings are reported. First, in the presence of exogenous lymphokines, resting CD8+ 2C cells gave strong proliferative responses to two alloantigens, Ld and Kbm11. In the absence of added lymphokines, however, CD8+ 2C cells responded only to Ld and not to Kbm11; Ld stimulated both interleukin 2 (IL-2) and IL-2 receptor (R) synthesis, whereas Kbm11 elicited only IL-2R synthesis. The primary response of CD8+ 2C cells was thus helper-independent (HI) to Ld but helper-dependent (HD) to Kbm11, presumably reflecting that Ld is a stronger antigen than Kbm11. Second, in contrast to CD8+ cells, CD8- 2C cells mounted only an HD and not an HI response to the strong Ld antigen; conversely, selecting for a minor subset of CD8hi cells enabled 2C cells to mount an HI response to the weak Kbm11 antigen. These findings, together with experiments with heterozygous vs. homozygous stimulator cells, suggest that HI and HD responses reflect differences in the overall avidity of T antigen presenting cell (APC) interaction: high-avidity interaction leads to strong intracellular signaling and an HI response, whereas low-avidity interaction causes weak signaling and an HD response; high-avidity T/APC interaction is heavily dependent on CD8 expression. Third, CD8 expression was found to be less important for CTL activity than for primary proliferative responses. Thus, in contrast to HI proliferative responses, CTL responses of 2C cells to Ld were CD8 independent. However, 2C lysis of Ld targets became strongly CD8 dependent in the presence of limiting doses of anti-TCR (1B2) antibody. Collectively, the data suggest that, both for T cell induction and the expression of effector function, CD8 molecules play a decisive role in augmenting TCR-mediated signaling, either by promoting TCR contact with antigen or delivering kinases (p56lck) to the TCR/CD3 complex, or both.
|
