New to MyHealth?
Manage Your Care From Anywhere.
Access your health information from any device with MyHealth. You can message your clinic, view lab results, schedule an appointment, and pay your bill.
ALREADY HAVE AN ACCESS CODE?
DON'T HAVE AN ACCESS CODE?
NEED MORE DETAILS?
MyHealth for Mobile
ANTI-SCID MOUSE REACTIVITY SHAPES THE HUMAN CD4(+) T-CELL REPERTOIRE IN HU-P8L-SCID CHIMERAS
ANTI-SCID MOUSE REACTIVITY SHAPES THE HUMAN CD4(+) T-CELL REPERTOIRE IN HU-P8L-SCID CHIMERAS JOURNAL OF EXPERIMENTAL MEDICINE TARYLEHMANN, M., Lehmann, P. V., SCHOLS, D., Roncarolo, M. G., Saxon, A. 1994; 180 (5): 1817-1827Abstract
Injecting human peripheral blood mononuclear cells into severe combined immunodeficient (SCID) mice results in long-term engraftment of human lymphocytes, of which > 98% are phenotypically mature, activated T cells. Here we have characterized the human T cells that populate such hu-PBL-SCID chimeras. We report that these human T cells do not mobilize Ca2+ after CD3 stimulation, i.e., their T cell receptor (TCR)-mediated signal transduction is deficient. Chimera-derived human T cells do not secrete lymphokines or undergo blastogenesis after CD3 stimulation, but proliferate in response to interleukin 2 (IL-2), defining the chimera derived human T cells as anergic. Anergy was seen in both the CD4+ and the CD8+ subpopulations. We established human T cell lines from chimeras. These T cells retained their anergic state for 1-2 mo in culture, after which they simultaneously regained the ability to mobilize Ca2+, secrete lymphokines, and to undergo blastogenesis following stimulation via the TCR. Once regaining proliferative responsiveness to CD3 stimulation, these CD4+ T cell lines displayed anti-SCID mouse reactivity and showed no specificity for recall antigens. All CD3-responsive CD4+ T cell clones obtained from such lines were SCID mouse specific, recognizing native major histocompatibility complex class II products on the murine cells. In contrast, chimera-derived human CD8+ cell lines and clones did not display detectable anti-mouse reactivity. The data show that the human T cell system in long term hu-PBL-SCID chimeras is nonfunctional due to both anergy and the limitation of the CD4+ repertoire to xenoreactive clones. The data suggest that long-term hu-PBL-SCID chimerism represents an atypical graft-versus-host reaction in which the human effector T cells become anergic in the murine environment.
View details for Web of Science ID A1994PP54300024
View details for PubMedID 7964463