Dynamics of memory T cell proliferation under conditions of heterologous immunity and bystander stimulation.
By examining adoptively transferred CSFE-labeled lymphocytic choriomeningitis virus (LCMV)-immune donor T cells in Thy-1 congenic hosts inoculated with viruses or with the cytokine inducer poly(I:C), strikingly different responses of bona fide memory T cells were found in response to different stimuli. Poly(I:C) (cytokine) stimulation caused a limited synchronized division of memory CD8 T cells specific to each of five LCMV epitopes, with no increase and sometimes a loss in number, and no change in their epitope hierarchy. Homologous LCMV infection caused more than seven divisions of T cells specific for each epitope, with dramatic increases in number and minor changes in hierarchy. Infections with the heterologous viruses Pichinde and vaccinia (VV) caused more than seven divisions and increases in number of T cells specific to some putatively cross-reactive but not other epitopes and resulted in substantial changes in the hierarchy of the LCMV-specific T cells. Hence, there can be memory T cell division without proliferation (i.e., increase in cell number) in the absence of Ag and division with proliferation in the presence of Ag from homologous or heterologous viruses. Heterologous protective immunity between viruses is not necessarily reciprocal, given that LCMV protects against VV but VV does not protect against LCMV. VV elicited proliferation of LCMV-induced CD8 and CD4 T cells, whereas LCMV did not elicit proliferation of VV-induced T cells. Thus, depending on the pathogen and the sequence of infection, a heterologous agent may selectively stimulate the memory pool in patterns consistent with heterologous immunity.
Kim
Sung-Kwon
SK
Department of Pathology, University of Massachusetts, Worcester, MA 01655, USA.
Brehm
Michael A
MA
Welsh
Raymond M
RM
Selin
Liisa K
LK
D019264:Adoptive Transfer; D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D024201:Bystander Effect / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation / Q000821:virology; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D006224:Cricetinae; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005452:Fluoresceins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D007156:Immunologic Memory / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D018655:Lymphocyte Count; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018052:Pichinde virus / Q000276:immunology; D011070:Poly I-C / Q000008:administration & dosage; D013388:Succinimides / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation / Q000821:virology
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D018984:Epitopes, T-Lymphocyte; D005452:Fluoresceins; D005456:Fluorescent Dyes; D013388:Succinimides; D011070:Poly I-C