First Author | Dalloul AH | Year | 1996 |
Journal | Eur J Immunol | Volume | 26 |
Issue | 1 | Pages | 213-8 |
PubMed ID | 8566069 | Mgi Jnum | J:112982 |
Mgi Id | MGI:3664160 | Doi | 10.1002/eji.1830260133 |
Citation | Dalloul AH, et al. (1996) CD4-negative cytotoxic T cells with a T cell receptor alpha/beta intermediate expression in CD8-deficient mice. Eur J Immunol 26(1):213-8 |
abstractText | Targeted disruption of the CD8 gene results in a profound block in cytotoxic T cell (CTL) development. Since CTL are major histocompatibility complex (MHC) class I restricted, we addressed the question of whether CD8-/- mice can reject MHC class I-disparate allografts. Studies have previously shown that skin allografts are rejected exclusively by T cells. We therefore used the skin allograft model to answer our question and grafted CD8-/- mice with skins from allogeneic mice deficient in MHC class II or in MHC class I (MHC-I or MHC-II-disparate, respectively). CD8-/- mice rejected MHC-I-disparate skin rapidly even if they were depleted of CD4+ cells in vivo (and were thus deficient in CD4+ and CD8+ T cells). By contrast, CD8+/+ controls depleted of CD4+ and CD8+ T cells in vivo accepted the MHC-I-disparate skin. Following MHC-I, but not MHC-II stimulation, allograft-specific cytotoxic activity was detected in CD8-/- mice even after CD4 depletion. A population expanded in both the lymph nodes and the thymus of grafted CD8-/- animals which displayed a CD4-8-3intermediateTCR alpha/betaintermediate phenotype. Indeed its T cell receptor (TCR) density was lower than that of CD4+ cells in CD8-/- mice or of CD8+ cells in CD8+/+ mice. Our data suggest that this CD4-8- T cell population is responsible for the CTL function we have observed. Therefore, MHC class I-restricted CTL can be generated in CD8-/- mice following priming with MHC class I antigens in vivo. The data also suggest that CD8 is needed to up-regulate TCR density during thymic maturation. Thus, although CD8 plays a major role in the generation of CTL, it is not absolutely required. |