PMID- 19713464 OWN - NLM STAT- MEDLINE DCOM- 20091117 LR - 20210206 IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 114 IP - 18 DP - 2009 Oct 29 TI - The human alloreactive CD4+ T-cell repertoire is biased to a Th17 response and the frequency is inversely related to the number of HLA class II mismatches. PG - 3947-55 LID - 10.1182/blood-2009-03-211896 [doi] AB - Estimates of precursor frequency and assessment of functional characteristics of alloreactive CD4+ T cells are all biased by the need for long-term culture. In this study, direct visualization of human alloreactive CD4+ T cells on the single-cell level was achieved using cell surface expression of CD154 as a tool for identification. The average frequency of alloreactive CD154+CD4+ T cells among peripheral blood CD4+ T cells was 0.1%, with half of the cells displaying a naive phenotype. The proliferation capacity and expression of cytokines after allogeneic stimulation resided in these CD154+CD4+ T cells. The repertoire of alloreactive CD4+ T cells was biased to a Th17 response, and on average 24% of alloreactive CD154+CD4+ memory T cells produced interleukin-17 (IL-17) after polyclonal stimulation. Unexpectedly, mixed cell cultures from human leukocyte antigen (HLA)-identical donors also generated alloreactive CD154+CD4+ T cells and yielded the highest frequency compared with HLA-nonidentical combinations. Therefore, reactivity to minor histocompatibility antigens between HLA-identical subjects appears to be relatively common. Alloreactive HLA-identical T cells did not proliferate or express cytokines, but were driven to proliferation in the presence of exogenous IL-2. FAU - Litjens, Nicolle H R AU - Litjens NH AD - Department of Internal Medicine, Division of Nephrology, Erasmus Medical Center, Rotterdam, The Netherlands. FAU - van de Wetering, Jacqueline AU - van de Wetering J FAU - van Besouw, Nicole M AU - van Besouw NM FAU - Betjes, Michiel G H AU - Betjes MG LA - eng PT - Journal Article DEP - 20090827 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antineoplastic Agents) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (IL2 protein, human) RN - 0 (Interleukin-2) RN - 147205-72-9 (CD40 Ligand) SB - IM MH - Antineoplastic Agents/pharmacology MH - *Blood Donors MH - CD40 Ligand MH - *Cell Proliferation MH - Cells, Cultured MH - Histocompatibility/*immunology MH - Histocompatibility Antigens Class II/*immunology MH - Humans MH - *Immunologic Memory MH - Interleukin-2/pharmacology MH - T-Lymphocytes, Helper-Inducer/*immunology MH - Time Factors EDAT- 2009/08/29 09:00 MHDA- 2009/11/18 06:00 CRDT- 2009/08/29 09:00 PHST- 2009/08/29 09:00 [entrez] PHST- 2009/08/29 09:00 [pubmed] PHST- 2009/11/18 06:00 [medline] AID - S0006-4971(20)39032-7 [pii] AID - 10.1182/blood-2009-03-211896 [doi] PST - ppublish SO - Blood. 2009 Oct 29;114(18):3947-55. doi: 10.1182/blood-2009-03-211896. Epub 2009 Aug 27.