CD4 and AIDS: A number of mechanisms have been suggested to contribute to immune activation in AIDS pathogenesis [3], [4], such as i) the innate and adaptive response to HIV and its antigens, ii) the direct effect of viral proteins on cell receptors like Env-CD4/CCR5 or TCR down-regulation by Nef, iii) the activation of TLRs by microbial products leaking from the damaged gut mucosa, iv) the frequency of opportunistic infections, v) increased levels of proinflammatory and pro-apoptotic cytokines, vi) depletion of CD4 T regulatory cells.