Defective protein tyrosine phosphoryiation and altered levels of p59 ^ and p56'< * in CD4

Early In HIV Infection, CD4+ lymphocytes exhibit the properties of an anergic state characterized by unresponslveness to mltogens or to TCR stimulation and by defective IL-2 production. As tyrosine phosphoryiation Is the earliest of the biochemical events Initiated by stimulation of CD3-TCR, we studied protein tyrosine phosphoryiation In purified CD4+ lymphocytes from 25 asymptomatic seropositlve patients (CD4 T cells>350/mm*) previously stimulated In vitro by Immobilized antl-CD3 mAb or by co-lmmoblllzed antl-CD3 and antl-CD28 mAbs. Purified CD4+ lymphocytes from HIV-lnfected patients exhibited defective early protein tyrosine phosphoryiation in response to CD3 activation when compared with normal subjects. This defect was observed mainly In patients In whom prollferatlve responses to Immobilized antl-CD3 ranged from 2 to 50% of control values obtained in healthy donors, and was frequently associated with Increased cellular levels of p59'>m and decreased cellular levels of p56**. Interestingly, these defects appeared to correlate with the degree of impairment In thymidlne incorporation. Since CD28 mAbs have been reported to enhance prollferatlve responses to the CD3-TCR pathway In cloned murine or human anergic models and to Induce tyrosine phosphoryiation In human T cells, w