Antigen-independent pathways of T-cell activation are functional in human immature thymocytes.
The signal requirements for proliferation of CD1+CD3- immature thymocytes have been studied in order to define whether this immature cell population could function despite the lack of the CD3/T-cell receptor complex. We found that CD1+CD3- cells proliferate upon stimulation with anti-CD28 monoclonal antibody as well as with a pair of anti-CD2 monoclonal antibodies in the presence of low doses (0.5 ng/ml) of phorbol-13-myristate-12-acetate and/or recombinant interleukin-2. A minor fraction of CD3+ cells (15%-20%) was also present in the proliferating cell population originating from CD1+CD3- thymocytes stimulated with phorbol-13-myristate-12-acetate and recombinant interleukin-2, either in the presence or in the absence of specific monoclonal antibodies. We further observed that the anti-CD3 monoclonal antibody did not induce the proliferation of CD1+CD3- cells, as expected, and efficiently triggered unfractionated or CD1+CD3+ thymocytes only if exogenous recombinant interleukin-2 was provided. Unexpectedly, we noted that highly purified (greater than 99%), CD1+CD3- immature thymocytes could mobilize calcium via CD3, besides CD2 and CD28 surface molecules, suggesting that a minor undetectable fraction (less than 1%) of CD3+ cells was still present in the purified CD3- population. Nevertheless, the preferential expansion of CD3-CD8+ cells (about one-third of proliferating cells) after triggering via CD28, and to a lesser extent via CD2, support the notion that the alternative pathways of T-cell activation are actually functional in CD1+CD3- immature thymocytes.
Poggi
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Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Zocchi
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MR
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D018949:Antigens, CD1; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D018801:CD2 Antigens; D018106:CD28 Antigens; D017252:CD3 Complex; D002454:Cell Differentiation; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D011971:Receptors, Immunologic / Q000276:immunology / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018949:Antigens, CD1; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D018106:CD28 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D013755:Tetradecanoylphorbol Acetate