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

Background It has been reported for the peripheral T cell repertoire t hat CD4 molecules may enhance adhesion between T cells and antigen pre senting cells and, through their physical association with T cell anti gen receptors, contribute to signal transduction. Objective The aims o f 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 antibodie s was examined for its ability to modulate T cell proliferation, cytok ine production and tolerance induction in house dust mite (THO and TH- 2) and influenza haemagglutinin (TH-1) specific human CD4+ T cell clon es all restricted by DRB11101 and isolated from dust mite allergic in dividuals. 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. F urthermore, IFN gamma and IL-4 production was differentially modulated depending on the specificity of the anti-CD4 antibody and the clone o f T cells. However, pretreatment of T cells with anti-CD4 antibody alo ne neither induced nor enhanced the susceptibility of T cells to pepti de mediated anergy. Conclusion Antigen recognition by different subset s of human CD4+ T cells has differential requirements on CD4, whereas the induction of specific anergy appeared to be independent of the fun ctions of CD4 molecules. Antigen induced IFN gamma production was more susceptible than IL-4 to the inhibitory effects of anti-CD4 antibodie s. Furthermore, it appeared that certain anti-CD4 antibodies can disso ciate antigen induced IFN gamma and IL-4 production, and may downregul ate IFN gamma synthesis without inhibiting antigen dependent prolifera tion.