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The neonatally T cell receptor 2-suppressed rat: lymphocyte subset composition and immune reactivity
1Genzentrum der Ludwig Maximilians Universität München, FRG.
Abstract:
Rats were injected intraperitoneally from birth on with a mouse monoclonal antibody (R73) to a constant determinant of the rat T cell receptor (TcR)2. Throughout the observation period (6 months), TcR2+ cells in peripheral lymphoid organs and blood were absent in treated animals with the exception of few (less than 10%) cells with a tenfold reduced TcR2 density; peripheral TcR2-CD3+ cells, i.e. most likely TcR1+ T cells, were increased in frequency. Among thymocyte subpopulations, only those expressing the TcR2 at a high level were reduced in number. The lack of a visible effect on immature thymocytes may, however, be due to the fact that despite high serum levels, thymic R73 determinants were incompletely saturated. Spleen and lymph node cells from TcR2-suppressed rats were completely unresponsive in mixed lymphocyte reaction (two fully allogeneic haplotypes tested) even in the presence of interleukin 2. Reactivity to the T cell mitogen concanavalin A was, in contrast, only partially reduced. Since rat TcR1 cells are activated by concanavalin A, these results suggest that the TcR1 cells present in TcR2-suppressed rats are functional, but do not respond to foreign major histocompatibility complex antigens at a high frequency, a finding of possible importance for immunosuppression with anti-TcR2 monoclonal antibody in human allografting. Neonatally TcR2-suppressed rats were unable to respond to the strong T-dependent antigen keyhole limpet hemocyanin administered intraperitoneally in alum with B. pertussis. Thus, in the absence of peripheral TcR2 cells, the numerically expanded TcR1 T cells are not capable of providing help for B lymphocytes.