Apart from other roles in providing immunologic help, the importance of the cytotoxic CD4+ T cell phenotype in direct tumor killing was first understood in pre-clinical models in which lymphopenic hosts (either RAG-deficient or lethally irradiated) transplanted with syngeneic melanoma tumor received naive, TCR-transgenic CD4+ T cells recognizing the TRP-1 antigen. Here, CD4 is linked to neoplasm.