The immunomodulatory role of CD4-positive cytotoxic T-lymphocytes in health and disease.

Among the CD4-positive (CD4+) T-lymphocytes a population exists which expresses cytolytic activity. These 'killer' cells belong to the T helper type 1 (Th1) subset and if activated, express Fas-ligand (FasL) which induces apoptosis in Fas-positive target cells. The major targets of these CD4+ cytotoxic T-lymphocytes (CTL) are cells of the immune system, such as T, B cells and macrophages which express Fas upon activation. Thus, CD4+ CTL play a major immunoregulatory part through the elimination of activated myeloid and lymphoid cells during and upon completion of an immune response. In certain diseases, such as in HIV-infection and some autoimmune disorders, the functional activity of CD4+ CTL is disturbed preferentially at the level of FasL-Fas interaction, further emphasizing their important immunoregulatory role. Furthermore, Fas-ligand expressing tumors can evade the attack of Fas-positive CD4+ CTL and other effector cells, thereby giving them an opportunity to expand.