The Correlation Between the Proliferative and the Cytotoxic Responses of Mouse Lymphocytes to Allogeneic Cells in Vitro

Abstract

Abstract The relationship between the antigen recognition phase (mixed lymphocyte culture) and the cytotoxic effector phase of a mouse allograft reaction in vitro has been studied. In addition, the responsiveness of thymus-derived (T) cell depleted and bone-marrow derived (B) cell enriched lymphocyte populations to alloantigens was investigated. Using CBA mouse spleen cells, there was a separation in time (48 hr) between the maximal proliferative response (3H-thymidine uptake) and the peak generation of cytotoxic lymphocytes as measured by a 51Cr release assay. Quantitation of the cytotoxic response obtained by using spleen cells of neonatal thymectomized (NnTx) mice or adult thymectomized lethally irradiated and bone marrow-protected (ATxBM) mice demonstrated that the cytotoxic allograft response may be useful as a functional test for residual mature T cells within a lymphocyte population. Spleen cells of congenitally athymic (“nude”) mice did not contain precursor cells of cytotoxic lymphocytes. However, they proliferated in the “one way” mixed lymphocyte culture as did spleen cells of NnTx or ATxBM mice. Evidence is given that the proliferation of nude spleen cells was due to dividing lymphocytes and not to contaminating erythroid or myeloid elements. It is concluded that in the mouse both B and T cells are capable of proliferation in vitro due to alloantigens. Whereas T cells differentiate into cytotoxic effector cells, B lymphocytes respond independently of helper cells (T lymphocytes) and the mitotic response may be part of a humoral response to alloantigens in vitro.