Physiological numbers of CD4+ T cells generate weak recall responses following influenza virus challenge.
Naive and recall CD4(+) T cell responses were probed with recombinant influenza A viruses incorporating the OVA OT-II peptide. The extent of OT-II-specific CD4(+) T cell expansion was greater following primary exposure, with secondary challenge achieving no significant increase in numbers, despite higher precursor frequencies. Adoptive transfer experiments with OT-II TCR-transgenic T cells established that the predominant memory set is CD62L(hi), whereas the CD62L(lo) precursors make little contribution to the recall response. Unlike the situation described by other investigators, in which the transfer of very large numbers of in vitro-activated CD4 effectors can modify the disease process, providing CD62L(hi) or CD62L(lo) OT-II-specific T cells at physiological levels neither enhanced virus clearance nor altered clinical progression. Some confounding effects of the transgenic model were observed, with decreasing primary expansion efficiency correlating with greater numbers of transferred cells. This was associated with increased levels of mRNA for the proapoptotic molecule Bim in cells recovered following high-dose transfer. However, even with very low numbers of transferred cells, memory T cells did not expand significantly following secondary challenge. A similar result was recorded in mice primed and boosted to respond to an endogenous IA(b)-restricted epitope derived from the influenza virus hemagglutinin glycoprotein. Depletion of CD8(+) T cells during secondary challenge generated an increased accumulation of OT-II-specific T cells but only at the site of infection. Taken together, significant expansion was not a feature of these secondary influenza-specific CD4 T cell responses and the recall of memory did not enhance recovery.
Thomas
Paul G
PG
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Paul.Thomas@stjude.org
Brown
Scott A
SA
Morris
Melissa Y
MY
Yue
Wen
W
So
Jenny
J
Reynolds
Cory
C
Webby
Richard J
RJ
Doherty
Peter C
PC
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology* / Q000637:transplantation / Q000821:virology; D002460:Cell Line; D049109:Cell Proliferation; D018920:Coculture Techniques; D004285:Dogs; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology*; D011948:Receptors, Antigen, T-Cell / Q000008:administration & dosage / Q000235:genetics
D011948:Receptors, Antigen, T-Cell