A novel activation pathway for mature thymocytes. Costimulation of CD2 (T,p50) and CD28 (T,p44) induces autocrine interleukin 2/interleukin 2 receptor-mediated cell proliferation.
Prior studies have shown that thymocytes, unlike peripheral T cells, do not proliferate in response to mitogenic combinations of anti-CD2 mAbs. The present study demonstrated that stimulation by a mitogenic anti-CD2 combination (9-1 plus 9.6) with anti-CD28 induced vigorous thymocyte proliferation in the absence of exogenous IL-2. This thymocyte proliferation was IL-2 dependent as shown by the complete inhibition using anti-IL-2-R mAbs. Induction of IL-2-R transcripts was detected in thymocytes stimulated by the anti-CD2 antibody combination alone or the anti-CD2 combination plus anti-CD28 antibody. However, induction of IL-2 transcripts was observed only in thymocytes triggered jointly by the anti-CD2 combination plus anti-CD28 antibodies. The double-negative (CD4-8-) or CD1+ thymocytes isolated by sorting or by panning were unresponsive to CD2/CD28 triggering. The same mitogenic signal could induce vigorous proliferation of thymocytes with a mature phenotype, i.e., CD3+CD4+ or CD3+CD8+ thymocytes. Immunofluorescence studies demonstrated that the majority of CD3+ thymocytes were CD28+, and most of the CD28+ cells were located in the medullary compartment of thymus. These results indicated that the T cell lineage surface molecules CD28 and CD2 are involved in the regulation of expansion and further differentiation of mature thymocytes.
D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D015152:Blotting, Northern; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology; D014158:Transcription, Genetic
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2