CD4-negative cytotoxic T cells with a T cell receptor alpha/beta intermediate expression in CD8-deficient mice.
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.
Dalloul
A H
AH
R.W. Johnson Pharmaceutical Research Institute, Toronto, Canada.
Ngo
K
K
Fung-Leung
W P
WP
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis*; D016827:CD8 Antigens / Q000235:genetics*; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection / Q000235:genetics; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000276:immunology*; D016038:Skin Transplantation / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification / Q000276:immunology* / Q000378:metabolism*
D015704:CD4 Antigens; D016827:CD8 Antigens; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta