Journal of Experimental Medicine, Vol 148, 478-489, Copyright © 1978 by Rockefeller University Press
Role of the H-2 complex in induction of T helper cells in vivo. I. Antigen-specific selection of donor T cells to sheep erythrocytes in irradiated mice dependent upon sharing of H-2 determinants between donor and host
J Sprent
When purified CBA lymph node T cells were mixed with sheep erythrocytes
(SRC) and filtered from blood to lymph through irradiated syngeneic mice
for 1-2 days, the donor cells lost their capacity to stimulate anti-SRC
responses by CBA B cells; the response to a third-party antigen (horse
erythrocytes) was unaffected and active suppression was not involved. This
process of specific negative selection to SRC also occurred when
semiallogeneic mice were used as filtration hosts. By contrast, when
allogeneic hosts were used the helper function of the donor cells was not
reduced; this applied to both primed and unprimed T cells. Studied with
congeneic resistant strains indicated that negative selection to SRC
occurred only when the donor and host shared H-2 determinants. Studies with
T cells depleted of alloreactive lymphocytes showed that negative selection
to SRC in irradiated F1 hybrid mice was followed by a stage of positive
selection where the donor cells gave greatly increased responses to the
injected antigen. Positive selection did not occur in H-2-different mice,
however, and the helper function of the donor cells remained unchanged. By
these parameters it was concluded that homozygous T helper cells have no
detectable capacity to recognize antigen in an H-2-different environment.