Functional responsiveness in vitro and in vivo of alpha/beta T cell receptors expressed by the B2A2 (J11d)- subset of CD4-8- thymocytes.
B2A2-CD4-8- cells represent a rare subpopulation of thymocytes normally comprising 0.5% of the total adult thymus. These cells are known to express CD3-associated T cell receptor (TcR) alpha/beta molecules. In the present study we have examined the functional capacity of alpha/beta heterodimers on B2A2-CD4-8- cells. In the presence of monoclonal antibody (mAb) specific for either murine CD3 or TcR expressing the V beta 8-encoded beta chain (F23.1), B2A2-CD4-8- cells proliferated. Such proliferation was blocked by mAb to interleukin 2 receptor (IL 2R), suggesting an autocrine mechanism involving IL 2 production and subsequent utilization. IL 2 and also IL 3 production by mAb-stimulated B2A2-CD4-8- cells was directly confirmed. Furthermore, a panel of B2A2-CD4-8- clones were derived to assess the role of the TcR in cytolysis. Many clones were isolated which killed Fc receptor-bearing P815 target cells only in the presence of F23.1 mAb. Finally, in vivo treatment of neonatal mice with F23.1 mAb resulted in a marked reduction of V beta 8+ B2A2-CD4-8- thymocytes. Collectively, these results indicate that the TcR alpha/beta complex on CD4-CD8-B2A2- cells is fully capable of transducing signals that lead to proliferation, lymphokine production and cytolysis in vitro, as well as to disappearance of this subset from the thymus in vivo.
Howe
R C
RC
Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.
Pedrazzini
T
T
MacDonald
H R
HR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte; D001666:Binding Sites, Antibody; D003602:Cytotoxicity, Immunologic; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell