Examination and characterization of murine neonatal allospecific immunological responses following fetal/newborn in vivo exposure to allogeneic lymphocytes

Date of Award




Degree Name

Doctor of Philosophy (Ph.D.)


Microbiology and Immunology

First Committee Member

Robert B. Levy - Committee Chair


Exposure to allogeneic lymphocytes can elicit a variety of immunological responses. To determine the consequences of such exposure in neonatal animals, sublethal numbers of allogeneic spleen cells were introduced into MHC disparate fetal/newborn animals permitting the potential for both donor anti-host and host anti-donor recognition. Recipient animals were found to generate enhanced CTL responses 3 and 6 weeks later specific for allogeneic antigens present on the donor spleen cells. Thus, despite proposed neonatal suppressor cell activity and an injection route (i.v.) associated with depressed allogeneic responses, priming events had occurred in these neonatal mice. Moreover, the in vivo events associated with these primed CTL responses could be induced by accessory cell depleted but, importantly, not T-cell depleted donor populations. These results demonstrate that the induction of primed CTL responses by recipient animals exposed to allogeneic cells within 24 hours of birth requires donor anti-recipient immune recognition. The events associated with the induction of primed CTL responses by the recipient animals must occur within the first week following injection. This was determined by examining the recipient animals for the presence of the injected allogeneic cells. Utilizing a highly sensitive detection assay, employing antigen specific CTL, allogeneic cells were detected in every animal examined 4 days following injection however, such cells were no longer detectable 7 days post injection. At this same time (i.e. 7 days) the enhanced expression of recipient MHC and Ly-6 products had indicated that immune activation had occurred in vivo.T$\sb{\rm H}$-accessory cell interactions, which are reportedly inefficient in neonatal mice, were subsequently examined to determine which specific T$\sb{\rm H}$-AC pathways were involved in the generation of the primed CTL responses. By depleting the appropriate accessory cell populations, primed CTL responses generated were found to involve both allogeneic and self-Ia restricted recipient T$\sb{\rm H}$-AC pathways. In total, these findings have shown that neonatal accessory cells can function in the induction of allospecific responses and indicate that exposure of newborn mice to allogeneic cells can result in primed CTL responses provided immunocompetent T-cells capable of recognizing and responding against recipient antigens are present within the donor inoculum.


Biology, Microbiology

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