CLONAL ANALYSIS OF CD4 MEDIATED ACCESSORY FUNCTION ON THE EFFECTOR ACTIVITY OF HUMAN CD4+ T-CELL SUBSETS

Background It has been reported for the peripheral T cell repertoire that CD4 molecules may enhance adhesion between T cells and antigen presenting cells and, through their physical association with T cell antigen receptors, contribute to signal transduction. Objective The aims of this study were to determine if the modulation of CD4 molecules had differential effects on T cell recognition, antigen induced cytokine (IL-4 and IFN gamma), release and the induction of specific anergy for human TH-0, TH-1 and TH-2 cells. Methods A panel of anti-CD4 antibodies was examined for its ability to modulate T cell proliferation, cytokine production and tolerance induction in house dust mite (THO and TH-2) and influenza haemagglutinin (TH-1) specific human CD4+ T cell clones all restricted by DRB1*1101 and isolated from dust mite allergic individuals. Results We observed that anti-CD4 antibodies may inhibit or enhance antigen mediated T cell proliferation, which may reflect the differential requirements of T cells for selective functions of CD4. Furthermore, IFN gamma and IL-4 production was differentially modulated depending on the specificity of the anti-CD4 antibody and the clone of T cells. However, pretreatment of T cells with anti-CD4 antibody alone neither induced nor enhanced the susceptibility of T cells to peptide mediated anergy. Conclusion Antigen recognition by different subsets of human CD4+ T cells has differential requirements on CD4, whereas the induction of specific anergy appeared to be independent of the functions of CD4 molecules. Antigen induced IFN gamma production was more susceptible than IL-4 to the inhibitory effects of anti-CD4 antibodies. Furthermore, it appeared that certain anti-CD4 antibodies can dissociate antigen induced IFN gamma and IL-4 production, and may downregulate IFN gamma synthesis without inhibiting antigen dependent proliferation.