Novel Human CD4+ T Lymphocyte Subpopulations Defined by CD300a/c Molecule Expression.

Abstract

CD300a and CD300c are leukocyte membrane glycoproteins encoded by genes in the CD300 complex on human chromosome 17. These molecules function as immunoregulatory molecules that initiate triggering and inhibitory responses following ligation with ligands. The CMRF-35 monoclonal antibody binds to an epitope common to both molecules, expressed on most human leukocyte populations, apart from B lymphocytes and a subpopulation of CD4+ and CD8+ T lymphocytes. We used it to study the distribution of the CD300a and CD300c molecules on peripheral blood CD4+ T lymphocytes and defined novel CD300a/c++ , CD300a/c+ and CD300a/c− CD4+ T lymphocyte subpopulations. Resting peripheral CD4+ T lymphocytes express CD300a mRNA and very low amounts of CD300c. Activation results in an initial decrease in CD300a gene expression before an increase in both CD300a and CD300c gene expression. The upregulated expression of these genes was associated with increased CMRF-35 binding to activated T lymphocytes. The CD300a/c− fraction of CD4+ T lymphocytes proliferated to a greater extent than the CD300a/c++ fraction, in response to mitogens or allogeneic antigen. The poor proliferation of the CD300a/c++CD4+ in response to mitogens was explained by increased apoptosis within this subpopulation. The recall antigen, tetanus toxoid, stimulated the CD300a/c++CD4+CD45RO+ but not the CD300a/c−CD4+CD45RO+ subpopulation. Resting CD300a/c++CD4+ lymphocytes express low levels of IFNγ mRNA. Within 18 hours following in vitro activation, CD300a/c++CD4+ lymphocytes express more IFNγ mRNA and protein compared to the CD300a/c−CD4+ lymphocytes, however, after 24 hours both the CD300a/c+ and CD300a/c− CD4+ T lymphocytes were able to produce IFNγ. Th1 and Th17 effector populations are found within the CD300a/c++CD4+ T lymphocyte population, whilst the Treg population are restricted to the CD300a/c−CD4+ T lymphocyte population. Thus, CD300a/c subdivides CD4+ subpopulations into functional populations with the potential to immunoregulate immune and allogeneic responses. We are currently monitoring these populations in allogeneic haemopoietic stem cell recipients.