Hypoproliferative human lamina propria T cells retain the capacity to secrete lymphokines when stimulated via CD2/CD28 pathways.
Human lamina propria (LP) T cells exhibit a reduced proliferative capacity in response to antigen-specific stimulation. To investigate the functional state of such hypoproliferative T cells, we determined the capacity of LP T cells to produce lymphokines when stimulated by monoclonal antibodies that crosslink either the TCR/CD3 complex or accessory pathway molecules (CD2,CD28). We found that TCR/CD3-mediated proliferative responses of LP T cells were greatly diminished when compared to peripheral blood (PB) T cells, but were largely restored when cells were preincubated in IL-2. Despite their proliferative hyporesponsiveness, LP T cells (as compared to PB T cells) secreted equal amounts of IL-2 and increased amounts of IFN-gamma, IL-4 and IL-5; these increased cytokine responses were most evident when cells were stimulated via the accessory pathways. In further studies, purified CD4+ LP T cells were compared with purified CD4+/CD45RO+ PB T cells (i.e., the PB T cell subset they most resemble). LP T cells produced significantly more IFN-gamma and IL-5 but less IL-4 than their CD45RO+ PB counterparts. Overall, LP T cells are unresponsive T cells following stimulation via the TCR/CD3 pathway but nevertheless retain the capacity to produce increased levels of TH1 and TH2-type lymphokines following stimulation via the CD2/CD28 accessory pathway; thus, they are best classified as modified "anergic" T cells.
Boirivant
M
M
Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Fuss
I
I
Fiocchi
C
C
Klein
J S
JS
Strong
S A
SA
Strober
W
W
D018801:CD2 Antigens / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology*; D002455:Cell Division; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D008222:Lymphokines / Q000378:metabolism*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D018801:CD2 Antigens; D018106:CD28 Antigens; D008222:Lymphokines; D017260:Receptor-CD3 Complex, Antigen, T-Cell