Cancer patients' lymphocytes contain CD3+ CD4+ cells that proliferate in response to autologous tumor cells in the presence of exogenous low-dose interleukin-2 and autologous accessory cells.

To see whether cancer patients possess CD3+ CD4+ lymphocytes able to proliferate in response to autologous tumor cells (Auto-Tu), this lymphocyte subset was isolated either by positive or negative selection, both methods resulting in highly enriched CD4+ populations. Unseparated and isolated CD3+ CD4+ lymphocytes were then assayed for proliferating activity in the presence or absence of various amounts of Auto-Tu, with or without recombinant interleukin-2 (IL-2) (1.5-15 U/ml) and DR+ adherent cells or E- lymphocytes as autologous accessory cells (Auto-AC). Isolated CD3+ CD4+ lymphocytes were stimulated by Auto-Tu alone in only 1 out of 12 cases. CD3+ CD4+ cells failed to proliferate significantly in response to low doses of IL-2 alone but the addition of Auto-Tu caused stimulation in 8 out of 12 cases (67%). The further addition of Auto-AC to Auto-Tu + IL-2 resulted in enhanced response of isolated CD3+ CD4+ lymphocytes in 6 out of 8 cases tested. When reactivities to Auto-Tu in the presence of IL-2 and IL-2 + Auto-AC were considered together, positive responses of CD3+ CD4+ lymphocytes were seen in 11 out of 12 cases (92%). On the other hand, unseparated lymphocytes were stimulated by Auto-Tu alone in none out of 12 cases. Unseparated lymphocytes, however, responded to IL-2 in 11 out of 12 cases; such a response was increased by the addition of Auto-Tu in only 2 cases. Moreover, the IL-2 proliferation of unseparated lymphocytes was suppressed in 4 and in 3 out of 12 cases tested when Auto-Tu or Auto-Tu + Auto-AC were added respectively. These data indicate that lymphocytes of cancer patients contain CD3+ CD4+ cells that are usually unable to proliferate in response to Auto-Tu only. This proliferation, however, occurs when low doses of exogenous IL-2 are present and can be further amplified by the addition of Auto-AC. No response of CD4+ cells is observed in the presence of DR+ Auto-AC + IL-2 except in 2 out of 7 cases tested (28%), suggesting an Auto-Tu-restricted reactivity of CD3+ CD4+ lymphocytes in the majority of cases.