CD4 and infection: The regulation of T lymphocyte-mediated immune response does not appear to prevent tissue damage generated by the inflammatory response to Leptospira. In CD4+ T lymphocytes of humans with severe leptospirosis, the production of TNF-α and other pro-inflammatory cytokines has been found to be higher than in those with the mild form of the disease, which indicates that these cytokines can be used as markers of severity in the immunological phase of infection [74].