Ym. Law et al., HUMAN CD4 RESTORES NORMAL T-CELL DEVELOPMENT AND FUNCTION IN MICE DEFICIENT IN MURINE CD4, The Journal of experimental medicine, 179(4), 1994, pp. 1233-1242
The ability of a human coreceptor to function in mice was investigated
by generating human CD4 (hCD4)-expressing transgenic mice on a mouse
CD4-deficient (mCD4-/-) background. From developing thymocyte to matur
ed T lymphocyte functions, hCD4 was shown to be physiologically active
. By examining the expansion and deletion of specific Vbeta T cell fam
ilies in mutated mice with and without hCD4, it was found that hCD4 ca
n participate in positive and negative selection. Mature hCD4 single p
ositive cells also were found in the periphery and they were shown to
restore MHC class II-restricted alloreactive and antigen-specific T ce
ll responses that were deficient in the mCD4 (-/-) mice. In addition,
these hCD4 reconstituted mice can generate a secondary immunoglobulin
G humoral response matching that of mCD4 wild-type mice. The fact that
human CD4 is functional in mice and can be studied in the absence of
murine CD4 should facilitate studies of human CD4 activity in general
and human immunodeficiency virus 1 gp120-mediated pathogenesis in acqu
ired immune deficiency syndrome specifically.