title: Quantitative analysis of the influenza virus-specific CD4+ T cell memory in the absence of B cells and Ig.
abstract: The role of B lymphocytes and their Ig product in the development and maintenance of virus-specific CD4+ T cells has been analyzed in mice homozygous for disruption of the Ig mu gene (mu MT). These mice lack mature B220+ B cells and do not secrete Ig, but generate normal CD8+ cytotoxic T lymphocyte responses and have no difficulty clearing the HKx31 influenza A virus from the infected respiratory tract. Sequential limiting dilution analysis of virus-specific CD4+ T cells established that the frequencies of IL-2-producing T helper cell precursors in the draining lymph nodes and/or spleen from 7 days to 6 mo after infection were essentially similar in mu MT and C57BL/6 (B6) mice. Ag presentation and processing mechanisms involving Ig or B cells are apparently not required to generate virus-specific T helper cell precursors, and Ag-Ig complexes on follicular dendritic cells are not essential for the persistence of virus-specific CD4+ T cell memory. The main difference was that the spleens of the mu MT mice were much smaller than those of the B6 controls, and greater numbers of CD4+ T cells were found consistently in the regional mediastinal lymph nodes. This could be the result of abnormal expression of the lymph node homing receptor (CD62L) on the mu MT CD4+ T cells. However, the profiles of CD62L expression over the long term were comparable for both total and virus-specific CD4+ T cells from the two groups. The diminished role of the mu MT spleen is thus more likely to reflect the absence of germinal centers and/or Ig rather than a disruption of CD62L-mediated T cell trafficking.
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Topham
authors.forename: R A
authors.initials: RA
authors.lastname: Tripp
authors.forename: A M
authors.initials: AM
authors.lastname: Hamilton-Easton
authors.forename: S R
authors.initials: SR
authors.lastname: Sarawar
authors.forename: P C
authors.initials: PC
authors.lastname: Doherty
mesh_terms: D000361:Agammaglobulinemia / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003433:Crosses, Genetic; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D018858:Germinal Center / Q000473:pathology; D007075:Immunoglobulin M / Q000172:deficiency* / Q000276:immunology; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D007156:Immunologic Memory; D016130:Immunophenotyping; D009980:Influenza A virus / Q000276:immunology*; D007376:Interleukin-2 / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000150:complications / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000473:pathology
chemical_list: D000914:Antibodies, Viral; D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; D007376:Interleukin-2