Survival of naive CD4 T cells: Roles of restricting versus selecting MHC class II and cytokine milieu

The diversity of naive CD4 T cells plays an important role in the adaptive immune response by ensuring the capability of responding to novel pathogens , In the past, it has been generally accepted that naive CD4 T cells are in trinsically long-lived; however, there have been studies suggesting some CD 4 T cells are short-lived. In this report, we identify two populations of n aive CD4 T cells: a long-lived population as well as a short-lived populati on, In addition, we identify two factors that contribute to the establishme nt of long-lived naive CD4 T cells. We confirm earlier findings that MHC cl ass LI interaction with the TCR on CD4 T cells is important for survival. F urthermore, we find that MHC class II alleles with the correct restriction element for Ag presentation mediate the peripheral survival of naive CD4 T cells more efficiently than other positively selecting alleles, regardless of the selecting MHC in the thymus, The second component contributing to th e survival of naive CD4 T cells is contact with the cytokines IL-4 and IL-7 . We fmd that the physiological levels of IL-4 and IL-7 serve to enhance th e MHC class II-mediated survival of naive CD4 T cells in vivo.