tetano
Editor, Senior Moderator
J Virol. 2012 Apr 24. [Epub ahead of print]
Single and co-expression of CXCR4 and CXCR5 identifies CD4 T helper cells in distinct lymph node niches during influenza infection.
Elsner RA, Ernst DN, Baumgarth N.
Source
Graduate Group in Microbiology.
Abstract
Influenza virus infection results in strong, mainly T-dependent, extrafollicular and germinal center B cell responses, which provide life-long humoral immunity against the homotypic virus strain. Follicular T helper (T(FH)) cells are key regulators of humoral immunity. Questions remain regarding the presence, identity and function of T(FH) subsets regulating early extrafollicular and later germinal center B cell responses. This study demonstrates that ICOS but not CXCR5 marks T cells with B helper activity induced by influenza virus infection and identifies germinal center T cells (T(GC)) as lymph node resident CD4(+)ICOS(+)CXCR4(+)CXCR5(+)PSGL-1(lo)PD-1(hi) cells. CXCR4 expression intensity further distinguished their germinal center light and dark zone location. This population emerged strongly in regional lymph nodes and with similar kinetics than germinal center B cells and were the only T(FH) subsets missing in influenza-infected, germinal center-deficient SAP-/- mice - mice that were shown previously to lack protective memory responses after secondary influenza challenge. Thus, indicting the non-redundant functions of CXCR4 and CXCR5 co-expressing CD4 helper cells in antiviral B cell immunity. CXCR4(+) single positive T cells, present in B cell-mediated autoimmunity and regarded as "extrafollicular" helper T cells, were rare throughout the response, despite prominent extrafollicular B cell responses, revealing fundamental differences in autoimmune- and infection-induced T-dependent B cell responses. While all ICOS(+) subsets induced similar antibody levels in vitro, CXCR5 single-positive T cells were superior in inducing B cell proliferation. The regulation of T cell localization, marked by single and co-expression of CXCR4 and CXCR5, might be an important determinant of T(FH) function.
PMID:
22532671
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22532671
Single and co-expression of CXCR4 and CXCR5 identifies CD4 T helper cells in distinct lymph node niches during influenza infection.
Elsner RA, Ernst DN, Baumgarth N.
Source
Graduate Group in Microbiology.
Abstract
Influenza virus infection results in strong, mainly T-dependent, extrafollicular and germinal center B cell responses, which provide life-long humoral immunity against the homotypic virus strain. Follicular T helper (T(FH)) cells are key regulators of humoral immunity. Questions remain regarding the presence, identity and function of T(FH) subsets regulating early extrafollicular and later germinal center B cell responses. This study demonstrates that ICOS but not CXCR5 marks T cells with B helper activity induced by influenza virus infection and identifies germinal center T cells (T(GC)) as lymph node resident CD4(+)ICOS(+)CXCR4(+)CXCR5(+)PSGL-1(lo)PD-1(hi) cells. CXCR4 expression intensity further distinguished their germinal center light and dark zone location. This population emerged strongly in regional lymph nodes and with similar kinetics than germinal center B cells and were the only T(FH) subsets missing in influenza-infected, germinal center-deficient SAP-/- mice - mice that were shown previously to lack protective memory responses after secondary influenza challenge. Thus, indicting the non-redundant functions of CXCR4 and CXCR5 co-expressing CD4 helper cells in antiviral B cell immunity. CXCR4(+) single positive T cells, present in B cell-mediated autoimmunity and regarded as "extrafollicular" helper T cells, were rare throughout the response, despite prominent extrafollicular B cell responses, revealing fundamental differences in autoimmune- and infection-induced T-dependent B cell responses. While all ICOS(+) subsets induced similar antibody levels in vitro, CXCR5 single-positive T cells were superior in inducing B cell proliferation. The regulation of T cell localization, marked by single and co-expression of CXCR4 and CXCR5, might be an important determinant of T(FH) function.
PMID:
22532671
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22532671