EFFECT OF ANTI-CD4 ON CD4 SUBSETS .1. ANTI-CD4 PREFERENTIALLY DELETESRESTING, NAIVE CD4 CELLS AND SPARES ACTIVATED CD4 CELLS

Anti-CD4 has been extensively studied in murine models of autoimmunity and transplantation. The timing of anti-CD4 administration in these s ystems is critical because anti-CD4 effectively blocks primary T-depen dent responses but does not diminish ongoing or memory responses in im munized animals. These differential effects suggest that anti-CD4 supp resses a subpopulation of CD4+ cells. We previously observed in vitro that simultaneous activation through TCR-T3 rescued CD4+ cells from an ti-CD4 elimination. From this we hypothesized that activated CD4+ cell s resisted the effects of anti-CD4. We now show that in vivo treatment with anti-CD4 preferentially eliminated resting, naive CD4+ cells rat her than memory and effector CD4+ cells. The CD4+ cells that remained after anti-CD4 treatment exhibited evidence of recent activation, beca use a higher percentage expressed IL-2R, regardless of subset phenotyp e. Moreover, Mls-1-primed, anti-CD4-treated mice showed a higher perce ntage of Vbeta6+ (Mls-1 reactive) CD4+ cells than either unprimed mice , anti-CD4-treated mice, or Mls-1-primed controls, implicating the imp ortance of recent activation. These anti-CD4-resistant cells also reta ined their functional abilities. T cells from BALB/c mice treated with anti-CD4 after Mls-1 immunization maintained their MLR proliferation against DBA/2 stimulator cells. In addition, anti-CD4 did not reduce T -dependent antibody responses in mice previously primed against the Ag cholera toxin or SRBC. Thus, activated CD4+ cells resist the suppress ive effects of anti-CD4. Our findings have critical implications for t he ongoing clinical trials using anti-CD4.